Pharmacokinetic Study of ADVATE 3000 IU in Previously Treated Patients With Severe Hemophilia A

The objective of this clinical study is to compare the pharmacokinetic parameters of 3000 IU Advate using one 3000 IU potency vial dissolved in 5 mL diluent with that of 3000 IU Advate using two vials of 1500 IU potency dissolved in 5 mL diluent each (administered in 10 mL diluent in total) in previously treated patients with severe hemophilia A (factor VIII level < 1%).

• Active Comparator: 1
  One infusion using a 3000 IU potency vial of Advate dissolved and administered in 5 mL diluent followed by a second infusion of two 1500 IU potency vials of Advate dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
  Intervention: Biological: Octocog alfa (recombinant human coagulation factor VIII) [ADVATE]
• Active Comparator: 2
  One infusion of two 1500 IU potency vials of Advate dissolved in 5 mL diluent each (administered in 10 mL diluent in total) followed by a second infusion of one 3000 IU potency vial of Advate dissolved and administered in 5 mL diluent
  Intervention: Biological: Octocog alfa (recombinant human coagulation factor VIII) [ADVATE]

Inclusion Criteria:

• Subject is 18 to 65 years old, at the time of screening
• Subject has provided signed informed consent
• Subject has severe hemophilia A, defined by a baseline FVIII level < 1% of normal, as tested at screening at the central laboratory
• Subject's weight is between 55-65 kg
• Subject was previously treated with FVIII concentrate(s) for a minimum of 150 exposure days prior to study entry
• If subject is HIV positive, he must be immunocompetent as determined with a CD4 count >= 200 cells/mm³ (CD4 count at screening)
• Subject is willing and able to comply with the requirements of the protocol

Exclusion Criteria:

• Subject has a detectable FVIII inhibitor at screening, with a titer >= 0.4 BU (Nijmegen modification of the Bethesda Assay) measured at the central laboratory
• Subject has a history of FVIII inhibitors with a titer >= 0.4 BU (by Nijmegen assay) or >= 0.5 BU (by Bethesda Assay) at any time prior to screening
• Subject has undergone a surgery within 21 days prior to screening or within 6 weeks prior to the anticipated first PK infusion
• Subject has an abnormal renal function (serum creatinine > 1.5 mg/dL)
• Subject has active hepatic disease (ALT or AST levels > 5 times the upper limit of normal)
• 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
• Subject has clinical and/or laboratory evidence of abnormal hemostasis from causes other than hemophilia A (eg, late-stage chronic liver disease, immune thrombocytopenia purpura)
• Subject is currently receiving, or is scheduled to receive during the course of the clinical study, an immunomodulating drug other than anti-retroviral chemotherapy (eg, alfa-interferon, or corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day)
• Subject has a known hypersensitivity to mouse or hamster proteins
• Subject has participated in another clinical study involving an investigational product or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product or investigational device during the course of this clinical study
• Subject is identified by the investigator as being unable or unwilling to cooperate with study procedures
• Subject is a member of the team conducting this clinical study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, or parents) as well as employees of the investigator or site personnel conducting the clinical study.