Aztreonam Aerosol to Treat Cystic Fibrosis Nasal Disease

This study is designed to explore the efficacy and safety of nasal aztreonam administered
using the Pari Sinus Nebulizer combined with oral Cayston aerosol therapy compared to placebo
on clinical and laboratory endpoints such as risk of antibiotic-resistant Pseudomonas
aeruginosa (PA), time to pulmonary infection exacerbation, nasal quality of life, pulmonary
function, nasal and lower airway cultures, and properties of mucus.

P. aeruginosa (PA) is a primary cause of lung infections in persons with cystic fibrosis (CF)
(1). Over the past decade, studies have shown that aerosolized antibiotics can reduce lower
respiratory bacterial load, decrease exacerbations of pulmonary disease, and in many patients
improve pulmonary function. Cayston (aztreonam) oral aerosol using the PARI Altera Nebulizer
System was approved by the FDA in February 2010 for CF patients 7 years of age or older with
PA (2). In 2011, 35.8% or patients in the National CF Patient Registry used Cayston for
treatment (3). Bacterial cultures suggest that the upper airways and lower airways of CF
patients are cross-infected by PA and that the paranasal sinuses can act as a bacterial
reservoir (4). There is improved post-transplanation patient survival for recipients that
undergo sinus surgery and daily nasal washes to reduce bacterial load (2).

Routine CF care does not generally include upper airway assessment. There are no published
studies evaluating the effect of aerosol antibiotics to treat nasal and sinus infections in
CF in combination with oral inhaled aerosol therapy to treat the lower airway disease.
However Mainz and colleagues published a case report that suggested that sinonasal
administration of tobramycin using the Pari Sinus nebulizer (Pari Corp, Starnberg, Germany)
delayed PA lower respiratory infection in a 12 year-old with CF who had chronic mucopurulent
rhinosinusitis (5) and studies in chronic obstructive pulmonary disease suggest that treating
upper airways can also improve coexistent lower airway disease.

Inclusion Criteria:

1. Males or females 7 years of age or older and able to perform pulmonary function
testing

2. Confirmed diagnosis of CF by the 1997 CF Consensus Conference criteria and followed by
the VCU or EVMS CF clinic

3. Presence of PA in 2 lower respiratory tract (sputum) cultures in the 24 months before
screening

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

5. All sexually active female subjects who are of childbearing potential must agree to
use an effective method of contraception (i.e.condoms or abstinence).

6. All sexually active female subjects must have a negative pregnancy test at screening
(V0).

7. Clinically stable determined by the study physician with no significant new
respiratory symptoms.

8. Presence of PA in nasal culture (swab or secretion) or sinus culture obtained in the
12 months before screening or at screening visit

Exclusion Criteria:

1. Use of oral, IV or inhaled antibiotics within 0 days before study other than low dose
azithromycin

2. Severe pulmonary disease with FEV1<30% predicted of baseline SpO2<0.90

3. ENT surgery within 6 months of screening

4. Allergy or documented adverse reaction to aztreonam

5. Epistaxis or significant (>30mL) hemoptysis in the past 6 months

6. Frequent (weekly or more frequently) or severe headaches

7. Subject is unlikely to comply with the procedures scheduled in the protocol

8. Subject participates in another clinical trial within 30 days prior to study entry

9. Subjects who have had a lung transplant will be excluded

10. Prisoners will be excluded

11. Non-English Speaking patients will be excluded