Pharmacokinetic Study of ARALAST (Human Alpha1- PI)
Condition: Alpha 1-Antitrypsin Deficiency
MeSH terms: Alpha 1-Antitrypsin Deficiency
Intervention: Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor; Dose of 60 mg/kg alpha1-proteinase inhibitor
Intervention description: Subjects meeting the eligibility criteria were randomized to receive either single dose ARALAST alpha1-proteinase inhibitor 60 mg/kg or single-dose ARALAST alpha1-proteinase inhibitor Fr. IV-1 60 mg/kg at 0.2 mL/kg/min during the first treatment period with crossover to the alternate study product during the second treatment period, with a minimum of 7 days between the two treatment periods.; Subjects meeting the eligibility criteria were randomized to receive either single dose ARALAST alpha1-proteinase inhibitor 60 mg/kg or single-dose ARALAST alpha1-proteinase inhibitor Fr. IV-1 60 mg/kg at 0.2 mL/kg/min during the first treatment period with crossover to the alternate study product during the second treatment period, with a minimum of 7 days between the two treatment periods.
Intervention MeSH terms: Protease Inhibitors; Alpha 1-Antitrypsin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Severe congenital Alpha1-Proteinase Inhibitor (Alpha1-PI) deficiency

Summary:

      The primary purpose of this study is to characterize the pharmacokinetic profile of
      intravenous Aralast Fraction (Fr.) IV-1, a sterile, stable, lyophilized preparation of
      functionally intact human Alpha1- Proteinase Inhibitor (α1-PI). This pharmacokinetic study
      will be a randomized controlled clinical trial with a cross-over design. Twenty-four subjects
      will be enrolled into the study. Overall study duration will be approximately 6-8 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject or subject´s legally authorized representative has provided written
             informed consent

          -  Subject is 18 years of age or older

          -  Subject has a documented, endogenous plasma Alpha1-PI level < 8 Micromolar

          -  Subject is of the genotype Pi*Z/Z, Pi*Z/Null, Pi*Null/Null, Pi*Malton/Z, or others,
             dependent on the approval by the Sponsor

          -  If the subject is female or of childbearing potential, the subject has a negative
             urine test for pregnancy within 7 days prior to first study product administration and
             agrees to employ adequate birth control measures for the duration of the study

          -  Laboratory results obtained at the screening visit, meeting the following criteria:

               -  Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) <= 2 times
                  the upper limit of normal (ULN)

               -  Serum total bilirubin <= 2 times ULN

               -  Proteinuria < +2 on dipstick analysis

               -  Serum creatinine <= 1.5 times ULN

               -  Absolute neutrophil count (ANC) >= 1500 cells/mm3

               -  Hemoglobin >= 10.0 g/dL

               -  Platelet count >= 10^5/mm3

          -  If the subject is treated with any respiratory medications, including inhaled
             bronchodilators and inhaled or oral corticosteroids, the subjects´ medication doses
             were unchanged for at least 14 days prior to first study product administration

          -  Nonsmoker for a minimum of 3 months prior to first study product administration

        Exclusion Criteria:

          -  The subject has received any Alpha1-PI augmentation therapy (including Aralast and
             investigational Alpha1-PIs, by any route including intravenous and inhaled) within 42
             days prior to first study product administration

          -  The subject has received an investigational drug or device within 1 month prior to
             first study product administration, or the subject is currently receiving an
             investigational drug

          -  The subject has a known selective immunoglobulin A (IgA) deficiency (IgA level < 15
             mg/dL) and/or antibody to IgA

          -  The subject has a pulmonary exacerbation or had a pulmonary exacerbation in the past
             14 days prior to first study product administration

          -  The subject is pregnant or lactating, or intends to become pregnant during the course
             of the study

          -  The subject has a 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