Pharmacokinetic Study of ADVATE Reconstituted in 2 mL Sterile Water for Injection
Condition: Hemophilia A
MeSH terms: Hemophilia A
Intervention: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)
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.
Intervention MeSH terms: Factor VIII
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 2 Years
Maximum age: 65 Years
Healthy volunteers: No

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.
    

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