Clinical trial NCT00952822: Pharmacokinetic Study of ADVATE Reconstituted in 2 mL Sterile Water for Injection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hemophilia A
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2009-08-06
Enrollment: 52
Sex: ALL
Minimum age (years): 2
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief 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

Primary outcomes:
measure: Area Under the Curve
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Secondary outcomes:
measure: Total Area Under the Curve
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Adjusted in Vivo Incremental Recovery
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion
measure: Terminal Half-life
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Weight-Adjusted Clearance
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Mean Residence Time
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Volume of Distribution at Steady State
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Maximum Plasma Concentration
timeFrame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
measure: Number and Severity of Infusion Site Reactions
timeFrame: Within 5 minutes pre-infusion up to 24 hours post-infusion
measure: Infusion Site Pain
timeFrame: Within 5 minutes post-infusion up to 24 hours post-infusion
Other outcomes:
Locations:
city: Washington
country: United States
state: District of Columbia
city: Atlanta
country: United States
state: Georgia
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Detroit
country: United States
state: Michigan
city: New Brunswick
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: