Pharmacokinetic Study of ADVATE Reconstituted in 2 mL Sterile Water for Injection
This study has been completed.
Sponsor:
Baxter Healthcare Corporation
Information provided by:
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT00952822
First received: August 4, 2009
Last updated: June 23, 2011
Last verified: June 2011
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Hemophilia A |
Biological: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII) |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label |
| 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 |
Resource links provided by NLM:
Further study details as provided by Baxter Healthcare Corporation:
Primary Outcome Measures:
- Area Under the Curve [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method
Secondary Outcome Measures:
- Total Area Under the Curve [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]Total AUC when the concentration is extrapolated to zero using the slope of the β-phase of the model
- Adjusted in Vivo Incremental Recovery [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion ] [ Designated as safety issue: No ]Increase in factor VIII concentration from pre- to post-infusion
- Terminal Half-life [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]Computed from the regression slope in the terminal phase of the model. Terminal half life is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%.
- Weight-Adjusted Clearance [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]Computed as the weight-adjusted dose divided by total AUC
- Mean Residence Time [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]Computed as total area under the moment curve divided by the total AUC. Total area under the first moment curve (AUMC) estimated by linear trapezoidal methods
- Volume of Distribution at Steady State [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]Computed as weight-adjusted clearance * mean residence time
- Maximum Plasma Concentration [ Time Frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion ] [ Designated as safety issue: No ]Maximal factor VIII concentration post-infusion
- Number and Severity of Infusion Site Reactions [ Time Frame: Within 5 minutes pre-infusion up to 24 hours post-infusion ] [ Designated as safety issue: Yes ]Infusion-related local reactions (including pain, tenderness, erythema, induration, and bruising) and severity were evaluated according to an FDA-defined grading scale (FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials; 2007).
- Infusion Site Pain [ Time Frame: Within 5 minutes post-infusion up to 24 hours post-infusion ] [ Designated as safety issue: Yes ]Pain was assessed by participants (≥5 years of age) on a visual analog scale (VAS) from 0 (no pain) to 100 (worst possible pain).
| Enrollment: | 52 |
| Study Start Date: | September 2008 |
| Study Completion Date: | December 2009 |
| Primary Completion Date: | October 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
ADVATE reconstituted in 2 mL sterile water for infusion
|
Biological: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)
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.
Other Name: ADVATE
|
|
Active Comparator: 2
ADVATE reconstituted in 5 mL sterile water for infusion
|
Biological: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)
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.
Other Name: ADVATE
|
Eligibility| Ages Eligible for Study: | 2 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00952822
Locations
| United States, District of Columbia | |
| Washington, District of Columbia, United States | |
| United States, Georgia | |
| Atlanta, Georgia, United States | |
| United States, Kentucky | |
| Lexington, Kentucky, United States | |
| Louisville, Kentucky, United States | |
| United States, Michigan | |
| Detroit, Michigan, United States | |
| United States, New Jersey | |
| New Brunswick, New Jersey, United States | |
| United States, New York | |
| New York, New York, United States | |
| United States, Ohio | |
| Cincinnati, Ohio, United States | |
| United States, Oregon | |
| Portland, Oregon, United States | |
| United States, Pennsylvania | |
| Philadelphia, Pennsylvania, United States | |
| United States, Texas | |
| Houston, Texas, United States | |
Sponsors and Collaborators
Baxter Healthcare Corporation
Investigators
| Study Director: | Wing-Yen Wong, MD | Baxter Healthcare Corporation |
More Information
No publications provided
| Responsible Party: | Wing Yen Wong, Baxter Healthcare Corporation |
| ClinicalTrials.gov Identifier: | NCT00952822 History of Changes |
| Other Study ID Numbers: | 060702 |
| Study First Received: | August 4, 2009 |
| Results First Received: | October 28, 2010 |
| Last Updated: | June 23, 2011 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Hemophilia A Blood Coagulation Disorders, Inherited Blood Coagulation Disorders Hematologic Diseases Coagulation Protein Disorders Hemorrhagic Disorders |
Genetic Diseases, Inborn Factor VIII Coagulants Hematologic Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 19, 2013