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 (Alpha1-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.

Condition	Intervention	Phase
Alpha 1-Antitrypsin Deficiency	Drug: ARALAST Fraction IV-1 Alpha1-Proteinase Inhibitor (ARALAST Fr. IV-1)	Phase I

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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

Please refer to this study by ClinicalTrials.gov identifier  NCT00242385

Australia, South Australia
      The Queen Elizabeth Hospital, Woodville,  South Australia,  Australia
      Royal Adelaide Hospital, Adelaide,  South Australia,  Australia
Australia, Victoria
      St. Vincent´s Hospital, Fitzroy,  Victoria,  Australia
Australia, Western Australia
      Sir Charles Gairdner Hospital, Nedlands,  Western Australia,  Australia
New Zealand
      Christchurch Hospital, Canterbury Respiratory Research Group, Christchurch,  New Zealand
      Waikato Hospital, Respiratory Department, Hamilton,  New Zealand
New Zealand, Auckland
      Middlemore Hospital, Otahuhu,  Auckland,  New Zealand

Study chairs or principal investigators

Jeff Garrett, MD,  Principal Investigator,  Middlemore Hospital, Otahuhu, Auckland, New Zealand   

Study ID Numbers:  460501
Last Updated:  December 8, 2005
Record first received:  October 19, 2005
ClinicalTrials.gov Identifier:  NCT00242385
Health Authority: United States: Food and Drug Administration; Australia: Human Research Ethics Committee; New Zealand: Health and Disability Ethics Committees
ClinicalTrials.gov processed this record on 2006-01-10