Aztreonam Lysine for Pseudomonas Infection Eradication Study

This is an open-label, multicenter study in pediatric patients age 3 months to less than 18
years with CF and newly detected PA pulmonary colonization/infection. The primary objective
of this study is to evaluate the proportion of patients with PA-negative cultures at all
time points during a 6-month monitoring period (through Day 196) after cessation of
Aztreonam for Inhalation Solution (AZLI) treatment; microbiological cultures will be
obtained at Baseline, Day 28 (end of AZLI treatment), Day 56 (1 month after completing AZLI
treatment), Day 112 (3 months after completing AZLI treatment), and Day 196 (6 months after
completing AZLI treatment).

Inclusion Criteria:

- Males or females age 3 months to less than 18 years

- Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria:

- Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis
test OR

- Abnormal nasal transepithelial potential difference test OR

- Two well-characterized, disease-causing genetic mutations in the CF
transmembrane conductance regulator (CFTR) gene AND

- One or more clinical features consistent with CF

- Documented new onset of positive lower respiratory tract culture (e.g., throat swab,
sputum, or BAL) for PA within 30 days of study entry (prior to screening visit)
defined as either first lifetime documented PA-positive culture OR PA recovered after
at least a 2 year history of PA-negative respiratory cultures (at least 2 cultures
per year)

- FEV1 ≥ 80% predicted at Screening Visit (subjects ≥ 6 years of age)

- Clinically stable with no evidence of significant respiratory symptoms or, if
obtained for clinical evaluation, no chest radiograph findings at screening that
would require administration of IV antipseudomonal antibiotics, oxygen
supplementation, or hospitalization

- All sexually active female subjects who are of childbearing potential must agree to
use a highly effective method of contraception during heterosexual intercourse
throughout the study. Females utilizing hormonal contraceptives as a birth control
method must have used the same method for at least 3 months prior to study drug
dosing

- Male subjects must agree to use barrier contraception (condom with spermicide) during
heterosexual intercourse from screening through to study completion and for 90 days
from the last dose of study investigational medicinal product

- Subjects and/or parent/guardian must be able to give written informed consent prior
to any study related procedure

Exclusion Criteria:

- Use of IV or inhaled antipseudomonal antibiotics within 2 years of study entry
(screening visit)

- Use of oral antipseudomonal antibiotics within 30 days of study entry (screening
visit)

- History of sputum or throat swab culture yielding Burkholderia spp. within 2 years
prior to screening visit

- History of local or systemic hypersensitivity to monobactam antibiotics

- History of intolerance to inhaled short acting beta 2 agonists

- History of lung transplantation

- History of AZLI (or Cayston®) administration

- Administration of any investigational drug or device within 28 days prior to
Screening Visit or within 6 half-lives of the investigational drug (whichever is
longer)

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

- Current requirement for daily continuous oxygen supplementation or requirement of
more than 2 L/minute at night

- Hospitalization for pulmonary-related illness within 28 days prior to Screening Visit

- Changes in or initiation of chronic azithromycin treatment within 28 days prior to
Screening Visit

- Changes in antimicrobial, bronchodilator (BD), corticosteroid, dornase alfa, or
hypertonic saline medications within 7 days prior to Screening Visit; for subjects on
a stable regimen of hypertonic saline (28 days on/28 days off), beginning or ending a
cycle of hypertonic saline is allowed

- Changes in physiotherapy technique or schedule within 7 days prior to Screening Visit

- Abnormal renal or hepatic function results at most recent test within the previous 12
months, defined as:

- AST or ALT > 5 times upper limit of normal (ULN), or

- Serum creatinine > 2 times ULN for age

- Pregnant or lactating females; a negative urine pregnancy test is required for all
female subjects of childbearing potential (unless surgically sterile), and
confirmatory serum pregnancy test in the event of an initial positive urine test
result

- Any serious or active medical or psychiatric illness (including drug or alcohol
abuse), which in the opinion of the investigator, would interfere with subject
treatment, assessment, or compliance with the protocol

- Presence of a condition or abnormality that would compromise the patient's safety or
the quality of study data, in the opinion of the investigator