Pharmacokinetic Study of ADVATE Reconstituted in 2 mL Sterile Water for Injection

This study has been completed.
Sponsor:
Information provided by:
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT00952822
First received: August 4, 2009
Last updated: June 23, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Hemophilia A
Biological: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • Area Under the Curve [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]
    Total AUC when the concentration is extrapolated to zero using the slope of the β-phase of the model

  • Adjusted in Vivo Incremental Recovery [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion ] [ Designated as safety issue: No ]
    Increase in factor VIII concentration from pre- to post-infusion

  • Terminal Half-life [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]
    Computed as the weight-adjusted dose divided by total AUC

  • Mean Residence Time [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]
    Computed as weight-adjusted clearance * mean residence time

  • Maximum Plasma Concentration [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]
    Maximal factor VIII concentration post-infusion

  • Number and Severity of Infusion Site Reactions [ Time Frame: Within 5 minutes pre-infusion up to 24 hours post-infusion ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Within 5 minutes post-infusion up to 24 hours post-infusion ] [ Designated as safety issue: Yes ]
    Pain was assessed by participants (≥5 years of age) on a visual analog scale (VAS) from 0 (no pain) to 100 (worst possible pain).


Enrollment: 52
Study Start Date: September 2008
Study Completion Date: December 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
ADVATE reconstituted in 2 mL sterile water for infusion
Biological: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)
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.
Other Name: ADVATE
Active Comparator: 2
ADVATE reconstituted in 5 mL sterile water for infusion
Biological: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)
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.
Other Name: ADVATE

  Eligibility

Ages Eligible for Study:   2 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00952822

Locations
United States, District of Columbia
Washington, District of Columbia, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Kentucky
Lexington, Kentucky, United States
Louisville, Kentucky, United States
United States, Michigan
Detroit, Michigan, United States
United States, New Jersey
New Brunswick, New Jersey, United States
United States, New York
New York, New York, United States
United States, Ohio
Cincinnati, Ohio, United States
United States, Oregon
Portland, Oregon, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Texas
Houston, Texas, United States
Sponsors and Collaborators
Baxter Healthcare Corporation
Investigators
Study Director: Wing-Yen Wong, MD Baxter Healthcare Corporation
  More Information

No publications provided

Responsible Party: Wing Yen Wong, Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT00952822     History of Changes
Other Study ID Numbers: 060702
Study First Received: August 4, 2009
Results First Received: October 28, 2010
Last Updated: June 23, 2011
Health Authority: United States: Food and Drug Administration

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
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 02, 2014