Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis and Chronic Burkholderia Species Infection

Inclusion Criteria:

1. Male or female ≥ 6 years of age

2. Subjects with CF as diagnosed by one of the following:

   • Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test
   • Documented sweat sodium ≥ 60 mmol/L
   • Two well characterized genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
   • Abnormal NPD with accompanying symptoms characteristic of CF

3. Chronic infection with Burkholderia spp. defined by:

   • One sputum culture positive for Burkholderia spp. within 6 months prior to baseline assessment,
   • At least 50% of sputum cultures collected at least one month apart over the previous 12 months prior to baseline assessment positive for Burkholderia spp. (minimum of 2 positive cultures), and
   • At least one positive sputum culture (obtained at any point in time) confirmed to be Burkholderia spp. by the CFF Burkholderia cepacia Research Laboratory and Repository at the University of Michigan (or equivalent Canadian reference laboratory)
4. Concomitant aerosolized antibiotic treatment: subjects receiving intermittent (alternating month on/month off) aerosolized antibiotic treatment are eligible, but must be at least 1 week into their off-treatment cycle at the time of baseline assessment. Subjects receiving continuous aerosolized antibiotic treatment will be eligible without restriction on their aerosolized antibiotic treatment
5. Chest radiograph, computed tomography (CT) or magnetic resonance imaging (MRI), (most recent, obtained within 90 days of screening) without significant acute findings (e.g., infiltrates [lobar or diffuse interstitial], pleural effusion, pneumothorax), and no significant intercurrent illness; chronic, stable findings (e.g., chronic scarring or atelectasis) are allowed
6. Subjects (and parent/guardian as required) must be able to provide written informed consent/assent prior to any study related procedures
7. Ability to perform reproducible pulmonary function tests
8. Sexually active females of childbearing potential must agree to use a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of study drug. A highly effective method of birth control is defined as a method that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), or a vasectomized partner

Exclusion Criteria:

1. Administration of any investigational drug or use of any investigational device within 28 days of randomization/baseline and within six half-lives of the investigational drug (whichever is longer)
2. Administration of AZLI treatment within the 28 days prior to randomization/baseline
3. Known local or systemic hypersensitivity to monobactam antibiotics
4. History of lung transplantation

5. Abnormal renal or hepatic function results at most recent test within the previous 90 days, defined as:

   • AST or ALT > 5 times upper limit of normal (ULN) range
   • Serum creatinine > 2 times ULN
6. Known portal hypertension or complications of CF hepatopathy
7. Positive urine pregnancy test (confirmed by serum pregnancy test) at screening; all women of childbearing potential will be tested
8. Female of childbearing potential who is lactating or not practicing a highly effective method of birth control as defined in Section 7.8
9. Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment or compliance with the protocol