Advate (rAHF-PFM): Pharmacokinetic comparison of 3000 IU Advate (rAHF-PFM) (using one 3000 IU potency vial) with 3000 IU Advate (rAHF-PFM) (using two 1500 IU potency vials) in previously treated patients with severe hemophilia A: a Phase IV, open-label, prospective, randomized, controlled, crossover, multiple center study - Advate 3000

• Conditions: severe hemophilia A; MedDRA version: 9.1Level: LLTClassification code 10060612Term: Hemophilia A

• Registration Number: EUCTR2008-007347-13-BG
• Lead Sponsor: Baxter Innovations GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-07-09
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 23

Inclusion Criteria

1. Subject is male 18 to 65 years old, at the time of screening.
2. The subject has provided signed informed consent.
3. The subject has severe hemophilia A, defined by a baseline FVIII level < 1% of normal (based on the chromogenic and the one stage activated partial thromboplastin time (aPTT) assays), as tested at screening at the central laboratory.
4. The subject's weight is between 55-65 kg.
5. The subject was previously treated with FVIII concentrate(s) for a minimum of 150 exposure days (as estimated by the investigator) prior to study entry.
6. If this subject is human immunodeficiency virus (HIV) positive, he must be immunocompetent as determined with a CD4 count >/= 200 cells/mm3 (CD4 count at screening).
7. Subject is willing and able to comply with the requirements of the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. The 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.
2. The 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.
3. The subject has undergone a surgery within 21 days prior to screening or within 6 weeks prior to the anticipated first PK infusion.
4. The subject has an abnormal renal function (serum creatinine >1.5 mg/dL).
5. The subject has active hepatic disease (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 5 times the upper limit of normal).
6. The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized RAtio (INR) > 1.4, as hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly, and history of esophageal varices.
7. The subject has clinical and/or laboratory evidence of abnormal hemostasis from causes other than hemophilia A (ed, late-stage chronic liver disease, or immune thrombocytopenia purpura).
8. The subject is currently receiving, or is scheduled to receive during the course of the study, an immunomodulating drug other than anti-retroviral chemotherapy (eg, alpha-interferon, or corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day).
9. The subject has a known hypersensitivity to mouse or hamster proteins.
10. Subject has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
11. The subject is identified by the investigator as being unable or unwilling to cooperate with study procedures.
12. The subject is a member of the team conducting this 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this clinical study is to compare the PK parameters of 3000 IU Advate using one 3000 IU potency vial dissolved in 5 ml diluent with that of 3000 IU Advate using two 1500 IU potency vials dissolved in 5 ml diluent each (administered in10 ml diluent in total) in PTPs with severe hemophilia A (FVIII level <1%);Secondary Objective: Evaluation and comparison of the percentage of subjects who experience IP related advserse events (AEs) between the treatment groups;Primary end point(s): The primary endpoint is the area under the plasma concentration versus time curve from 0 to 48 hours (AUC 0-48h)