Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa
Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa
The purpose of this study was to evaluate the safety and efficacy of aztreonam for inhalation
 solution (AZLI) in patients with cystic fibrosis (CF) and lung infection due to Pseudomonas
 aeruginosa (PA).
Patients with CF often have lung infections that occur repeatedly or worsen over time. The
 lung infections are often caused by a bacteria called PA. Treatment with antibiotics can stop
 or slow down the growth of the bacteria. The antibiotics may be given by mouth, intravenously
 (IV), or by inhalation as a mist. The purpose of this study was to evaluate the safety and
 efficacy of aztreonam for inhalation solution (AZLI), an investigational formulation of the
 antibiotic administered using the eFlow® Electronic Nebulizer by PARI GmbH, in CF patients
 with PA.

 In this study, participants were screened for eligibility at Visit 1 (Day -42) and returned
 to the center for Visit 2 after a 14-day evaluation period. At Visit 2 (Day -28),
 participants began a 28-day course of open-label Tobramycin Inhalation Solution (TIS). At
 Visit 3 (Day 0), following completion of the 28-day course of TIS, participants began
 randomized, blinded treatment with either AZLI twice a day (BID) or three times a day (TID)
 or placebo BID or TID, and continued treatment for a total of 28 days, with a clinic visit at
 Day 14 (Visit 4) and at the end of treatment (Visit 5 [Day 28]). Participants returned for
 visits every 2 weeks for 8 weeks after the end of the blinded treatment (Visits 6 to 9 [Days
 42 to 84]).

 Two hundred and forty-seven participants were treated in the TIS phase of this study. Two
 hundred and eleven subjects completed the TIS phase and were treated in the
 placebo-controlled phase with study drug (AZLI or placebo).
Inclusion Criteria:

 -  CF as diagnosed by:

 1. Documented sweat chloride greater than or equal to 60 mEq/L by quantitative
 pilocarpine iontophoresis test; or

 2. Two well-characterized genetic mutations in the cystic fibrosis transmembrane
 conductance regulator (CFTR) gene; or

 3. Abnormal nasal potential difference with accompanying symptoms characteristic of
 CF.

 -  PA present in expectorated sputum or throat swab culture at Screening.

 -  Participants must have received three or more courses of TIS within the previous 12
 months.

 -  Participants on chronic azithromycin must have had no change in regimen in the
 previous 3 months and must have had a need for TIS and/or additional antipseudomonal
 therapy since initiation of azithromycin.

 -  Forced expiratory volume in 1 second (FEV1) between (and including) 25% and 75%
 predicted at Screening.

 -  Ability to perform reproducible pulmonary function tests.

 -  Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at
 Screening.

 Exclusion Criteria:

 -  Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg
 prednisone a day or 20 mg prednisone every other day.

 -  History of sputum or throat culture swab yielding Burkholderia cepacia in the past 2
 years.

 -  History of daily continuous oxygen supplementation or requirement for more than 2
 liters/minute at night.

 -  Administration of any investigational drug or device within 28 days of Screening
 (Visit 1) or within 6 half-lives of the investigational drug (whichever was longer).

 -  Known local or systemic hypersensitivity to monobactam antibiotics.

 -  Inability to tolerate inhalation of a short acting Beta-2 agonist.

 -  Changes in antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid
 medications within 7 days before Screening or between Screening and the next visit.

 -  Changes in physiotherapy technique or schedule within 7 days before Screening or
 between Screening and the next visit.

 -  History of lung transplantation.

 -  A chest X-ray indicating abnormal findings at Screening or within the previous 90
 days.

 -  Abnormal renal or hepatic function or serum chemistry at Screening (aspartate
 aminotransferase [AST], alanine aminotransferase [ALT] greater than 5 times the upper
 limit of normal range; Creatinine greater than 2 times the upper limit of normal
 range).

 -  Positive pregnancy test at Screening.

 -  Female of childbearing potential who was lactating or in the opinion of the
 investigator was not practicing acceptable birth control.

 -  Any serious or active medical or psychiatric illness, which in the opinion of the
 investigator would have interfered with participant treatment, assessment, or
 compliance with the protocol.