Pharmacokinetic Study of ADVATE 3000 IU in Previously Treated Patients With Severe Hemophilia A
Condition: Hemophilia A
MeSH terms: Hemophilia A
Intervention: Octocog alfa (recombinant human coagulation factor VIII) [ADVATE]
Intervention description: Participants will receive 3000 IU Advate using one 3000 IU potency vial dissolved in 5 mL diluent followed by two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total) or the alternate sequence
Intervention MeSH terms: Factor VIII
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: Male
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      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%).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant is 18 to 65 years old, at the time of screening

          -  Participant has provided signed informed consent

          -  Participant has severe hemophilia A, defined by a baseline FVIII level < 1% of normal,
             as tested at screening at the central laboratory

          -  Participant's weight is between 55-65 kg

          -  Participant was previously treated with FVIII concentrate(s) for a minimum of 150
             exposure days prior to study entry

          -  If Participant is HIV positive, he must be immunocompetent as determined with a CD4
             count ≥ 200 cells/mm³ (CD4 count at screening)

          -  Participant is willing and able to comply with the requirements of the protocol

        Exclusion Criteria:

          -  Participant has a detectable FVIII inhibitor at screening, with a titer ≥ 0.4 Bethesda
             unit (BU) (Nijmegen modification of the Bethesda Assay) measured at the central
             laboratory

          -  Participant 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

          -  Participant has undergone a surgery within 21 days prior to screening or within 6
             weeks prior to the anticipated first pharmacokinetics(PK) infusion

          -  Participant has an abnormal renal function (serum creatinine > 1.5 mg/dL)

          -  Participant has active hepatic disease (alanine aminotransferase (ALT) or aspartate
             aminotransferase (AST) levels >5 times the upper limit of normal)

          -  Participant 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

          -  Participant has clinical and/or laboratory evidence of abnormal hemostasis from causes
             other than hemophilia A (eg, late-stage chronic liver disease, immune thrombocytopenia
             purpura)

          -  Participant 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)

          -  Participant has a known hypersensitivity to mouse or hamster proteins

          -  Participant 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

          -  Participant is identified by the investigator as being unable or unwilling to
             cooperate with study procedures

          -  Participant 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.