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Completed

NCT Number: NCT00952822

Pharmacokinetic Study of ADVATE Reconstituted in 2 mL Sterile Water for Injection

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.

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Key information

Conditions

Hemophilia A Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Coagulation Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders

Age range

2 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Washington D.C., District of Columbia, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)

Biological

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 names: ADVATE

Primary outcomes

  1. Area Under the Curve

    Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

    Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method

Secondary outcomes

  1. Total Area Under the Curve

    Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

    Total AUC when the concentration is extrapolated to zero using the slope of the β-phase of the model

  2. Adjusted in Vivo Incremental Recovery

    Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion

    Increase in factor VIII concentration from pre- to post-infusion

  3. Terminal Half-life

    Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

    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%.

  4. Weight-Adjusted Clearance

    Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

    Computed as the weight-adjusted dose divided by total AUC

  5. Mean Residence Time

    Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

    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

  6. Volume of Distribution at Steady State

    Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

    Computed as weight-adjusted clearance * mean residence time

  7. Maximum Plasma Concentration

    Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

    Maximal factor VIII concentration post-infusion

  8. Number and Severity of Infusion Site Reactions

    Time frame: Within 5 minutes pre-infusion up to 24 hours post-infusion

    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).

  9. Infusion Site Pain

    Time frame: Within 5 minutes post-infusion up to 24 hours post-infusion

    Pain was assessed by participants (≥5 years of age) on a visual analog scale (VAS) from 0 (no pain) to 100 (worst possible pain).

Sponsors and collaborators

Lead sponsor

Baxalta now part of Shire

Industry

Registry information

Official study 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

Important dates

Study start
2008
Primary completion
2009
Study completion
2009
First posted
Aug 6, 2009
Registry last updated
May 24, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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