Pharmacokinetic Study of ARALAST (Human Alpha1- PI)

Single-Dose, Double-Blind, Crossover Study to Evaluate the Pharmacokinetic Comparability of ARALAST Fraction IV-1 Alpha1-Proteinase Inhibitor (ARALAST Fr. IV-1) and ARALAST

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.

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