The purpose of this randomized, double-blind, placebo-controlled study is to evaluate the short-term safety of inhaled recombinant alpha 1-antitrypsin (rAAT) in subjects with alpha 1-antitrypsin deficiency. The subjects are randomized to receive placebo or one of 4 doses of rAAT. The 4 doses are tested in a consecutive manner from lowest to highest.

Condition	Intervention	Phase
alpha 1-Antitrypsin Deficiency	Drug: Aerosolized, Recombinant Alpha 1-Antitrypsin	Phase I

Further Study Details: 

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

Criteria

Inclusion Criteria:

• Male or female 18 years of age or older
• Endogenous plasma AAT levels < 11 µM (< 80 mg/dL)
• Baseline forced expiratory volume at one second (FEV1) that is >= 50% of predicted, measured 30 minutes after a short-acting inhaled bronchodilator
• Baseline arterial oxygen percent saturation (SaO2) within the normal limits for the individual study site
• For subjects receiving an inhaled corticosteroid, β-2 agonist (eg, albuterol via metered dose inhaler [MDI]) or anticholinergic bronchodilator (eg, ipratropium bromide), treatment on a stable dose for at least 14 days prior to randomization
• If female of childbearing potential, negative urine pregnancy test within 3 days prior to randomization and agreement to employ adequate birth control measures
• No clinically significant abnormalities detected on a 12-lead electrocardiogram (ECG) performed no more than 7 days prior to randomization
• Baseline laboratory results, obtained no more than 7 days prior to randomization, meeting the following criteria:
• Serum aspartate transaminase (AST) and alanine transaminase (ALT) <= 2 times upper limit of normal range (ULN)
• Serum total bilirubin <= 2 times ULN
• < 2+ proteinuria on urine dipstick
• Serum creatinine <= 1.5 times ULN
• Absolute neutrophil count >= 1500 cells/mm3
• Hemoglobin >= 10.0 g/dL
• Platelet count >= 100,000/mm3
• Signed informed consent

Exclusion Criteria:

• Clinically significant pulmonary impairment, other than emphysema and/or chronic bronchitis
• Clinically significant cardiac, hemostatic, or neurologic impairment, or other significant medical condition that, in the opinion of the investigator, would affect subject safety or compliance
• Psychiatric or cognitive disturbance or illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance
• Acute exacerbation of emphysema (as defined in Section 8.5.10) within 28 days prior to randomization
• Pregnancy or lactation
• Known history of allergy to yeast products
• Medical history precluding the use of epinephrine or other rescue medication for treatment of anaphylaxis
• Use of antihistamines within 7 days prior to randomization
• Use of oral steroids, beta-blockers, or tricyclic antidepressants within 28 days prior to randomization
• Use of another investigational drug or investigational device within 28 days prior to randomization
• Any upper or lower respiratory infection within 28 days prior to randomization

Colorado
      National Jewish Medical and Research Center, Denver,  Colorado,  80206,  United States
Florida
      Shands Hospital at the University of Florida, Gainesville,  Florida,  32610,  United States
Ohio
      Cleveland Clinic Foundation, Department of Pulmonary and Critical Care Medicine, Cleveland,  Ohio,  44195,  United States
Texas
      The University of Texas Health Science Center at Tyler, Tyler,  Texas,  75708-3154,  United States

Study chairs or principal investigators

Mark Brantly, MD,  Principal Investigator,  Shands Hospital at the University of Florida   

Study ID Numbers:  410103
Last Updated:  September 12, 2005
Record first received:  September 8, 2005
ClinicalTrials.gov Identifier:  NCT00161707
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-09-13