Back to resultsPharmacokinetic Study of ADVATE Reconstituted in 2 mL Sterile Water for Injection
Primary Purpose
Hemophilia A
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)
Sponsored by
About this trial
This is an interventional other trial for Hemophilia A
Eligibility Criteria
Inclusion Criteria:
- The subject or subject's legally authorized representative has provided written informed consent
- The subject has severe hemophilia A as defined by a baseline FVIII activity <= 1% of normal; tested at screening
- The adolescent/adult subject has a documented history of at least 150 exposure days to FVIII concentrates (either plasma-derived or recombinant), and the pediatric subject has at least 50 exposure days
- The subject is >= 12 to <= 65 years of age for the complete pharmacokinetic assessment and >= 2 to < 12 years for the incremental recovery assessment The subject has a Karnofsky performance score > 60
- The subject is human immunodeficiency virus negative (HIV-) or HIV+ with stable CD4 count >= 200 cells/mm³ (CD4 count determined at screening, if necessary)
Exclusion Criteria:
- The subject has a known hypersensitivity to mouse or hamster proteins or to FVIII concentrates
- The subject has a history of FVIII inhibitors with titer >= 0. 5 BU (Bethesda Assay) or >= 0.4 BU (Nijmegen modification of the Bethesda Assay) any time prior to screening
- The subject has a detectable FVIII inhibitor at screening, >= 0.4 BU (Nijmegen modification of the Bethesda Assay), in the central laboratory
- The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) > 1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices
- The subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (e.g. qualitative platelet defect or Von Willebrand Disease)
- The subject has received another investigational product within 30 days of enrollment
- The subject's clinical condition may require major or moderate surgery (estimated blood loss > 500 mL) during the period of participation in the study
- Subjects with clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance
- The subject is a female of childbearing potential with a positive pregnancy test at screening
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
1
2
Arm Description
ADVATE reconstituted in 2 mL sterile water for infusion
ADVATE reconstituted in 5 mL sterile water for infusion
Outcomes
Primary Outcome Measures
Area Under the Curve
Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method
Secondary Outcome Measures
Total Area Under the Curve
Total AUC when the concentration is extrapolated to zero using the slope of the β-phase of the model
Adjusted in Vivo Incremental Recovery
Increase in factor VIII concentration from pre- to post-infusion
Terminal Half-life
Computed from the regression slope in the terminal phase of the model. Terminal half life is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%.
Weight-Adjusted Clearance
Computed as the weight-adjusted dose divided by total AUC
Mean Residence Time
Computed as total area under the moment curve divided by the total AUC. Total area under the first moment curve (AUMC) estimated by linear trapezoidal methods
Volume of Distribution at Steady State
Computed as weight-adjusted clearance * mean residence time
Maximum Plasma Concentration
Maximal factor VIII concentration post-infusion
Number and Severity of Infusion Site Reactions
Infusion-related local reactions (including pain, tenderness, erythema, induration, and bruising) and severity were evaluated according to an FDA-defined grading scale (FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials; 2007).
Infusion Site Pain
Pain was assessed by participants (≥5 years of age) on a visual analog scale (VAS) from 0 (no pain) to 100 (worst possible pain).
Full Information
NCT ID
NCT00952822
First Posted
August 4, 2009
Last Updated
April 28, 2021
Sponsor
Baxalta now part of Shire
1. Study Identification
Unique Protocol Identification Number
NCT00952822
Brief Title
Pharmacokinetic Study of ADVATE Reconstituted in 2 mL Sterile Water for Injection
Official Title
A Phase 1, Prospective, Randomized, Crossover Study to Compare the Pharmacokinetics and Safety of rAHF-PFM Reconstituted in 2 mL Versus 5 mL SWFI in Previously Treated Severe Hemophilia A Patients
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
August 8, 2008 (Actual)
Primary Completion Date
October 23, 2009 (Actual)
Study Completion Date
October 23, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxalta now part of Shire
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine the pharmacokinetics and safety of Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM) reconstituted in 2 mL sterile water for injection (SWFI) and compare with those of rAHF-PFM reconstituted in 5 mL of SWFI.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
ADVATE reconstituted in 2 mL sterile water for infusion
Arm Title
2
Arm Type
Active Comparator
Arm Description
ADVATE reconstituted in 5 mL sterile water for infusion
Intervention Type
Biological
Intervention Name(s)
Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)
Other Intervention Name(s)
ADVATE
Intervention Description
Subjects are randomized to receive an infusion of rAHF-PFM reconstituted in 2 mL sterile water for infusion (SWFI) followed (after a wash-out period) by rAHF-PFM reconstituted in 5 mL SWFI or in 5 mL then 2 mL SWFI(cross-over design). Each subject will receive 2 infusions.
Primary Outcome Measure Information:
Title
Area Under the Curve
Description
Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Secondary Outcome Measure Information:
Title
Total Area Under the Curve
Description
Total AUC when the concentration is extrapolated to zero using the slope of the β-phase of the model
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Title
Adjusted in Vivo Incremental Recovery
Description
Increase in factor VIII concentration from pre- to post-infusion
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion
Title
Terminal Half-life
Description
Computed from the regression slope in the terminal phase of the model. Terminal half life is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%.
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Title
Weight-Adjusted Clearance
Description
Computed as the weight-adjusted dose divided by total AUC
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Title
Mean Residence Time
Description
Computed as total area under the moment curve divided by the total AUC. Total area under the first moment curve (AUMC) estimated by linear trapezoidal methods
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Title
Volume of Distribution at Steady State
Description
Computed as weight-adjusted clearance * mean residence time
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Title
Maximum Plasma Concentration
Description
Maximal factor VIII concentration post-infusion
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Title
Number and Severity of Infusion Site Reactions
Description
Infusion-related local reactions (including pain, tenderness, erythema, induration, and bruising) and severity were evaluated according to an FDA-defined grading scale (FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials; 2007).
Time Frame
Within 5 minutes pre-infusion up to 24 hours post-infusion
Title
Infusion Site Pain
Description
Pain was assessed by participants (≥5 years of age) on a visual analog scale (VAS) from 0 (no pain) to 100 (worst possible pain).
Time Frame
Within 5 minutes post-infusion up to 24 hours post-infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The subject or subject's legally authorized representative has provided written informed consent
The subject has severe hemophilia A as defined by a baseline FVIII activity <= 1% of normal; tested at screening
The adolescent/adult subject has a documented history of at least 150 exposure days to FVIII concentrates (either plasma-derived or recombinant), and the pediatric subject has at least 50 exposure days
The subject is >= 12 to <= 65 years of age for the complete pharmacokinetic assessment and >= 2 to < 12 years for the incremental recovery assessment The subject has a Karnofsky performance score > 60
The subject is human immunodeficiency virus negative (HIV-) or HIV+ with stable CD4 count >= 200 cells/mm³ (CD4 count determined at screening, if necessary)
Exclusion Criteria:
The subject has a known hypersensitivity to mouse or hamster proteins or to FVIII concentrates
The subject has a history of FVIII inhibitors with titer >= 0. 5 BU (Bethesda Assay) or >= 0.4 BU (Nijmegen modification of the Bethesda Assay) any time prior to screening
The subject has a detectable FVIII inhibitor at screening, >= 0.4 BU (Nijmegen modification of the Bethesda Assay), in the central laboratory
The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) > 1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices
The subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (e.g. qualitative platelet defect or Von Willebrand Disease)
The subject has received another investigational product within 30 days of enrollment
The subject's clinical condition may require major or moderate surgery (estimated blood loss > 500 mL) during the period of participation in the study
Subjects with clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance
The subject is a female of childbearing potential with a positive pregnancy test at screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
City
Washington
State/Province
District of Columbia
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Lexington
State/Province
Kentucky
Country
United States
City
Louisville
State/Province
Kentucky
Country
United States
City
Detroit
State/Province
Michigan
Country
United States
City
New Brunswick
State/Province
New Jersey
Country
United States
City
New York
State/Province
New York
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Houston
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Pharmacokinetic Study of ADVATE Reconstituted in 2 mL Sterile Water for Injection
We'll reach out to this number within 24 hrs