Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With CF

This study is a prospective, randomized, double-blinded, placebo-controlled trial of
azithromycin 500mg taken orally thrice weekly vs. placebo in subjects with cystic fibrosis
and chronic airway infection with P. aeruginosa who are utilizing chronic inhaled tobramycin
therapy. It will include approximately 120 subjects able to complete a primary 6-week study
phase. Subjects will be at least 12 years old with a baseline FEV1 between 25-100% predicted.
Subjects will continue to use clinically prescribed inhaled tobramycin cycled on/off every 4
weeks. They will be provided over-encapsulated azithromycin 500mg tablets or placebo during
the primary study phase. An optional extension phase will be offered to all subjects
completing the primary 6-week study. This 8-week extension phase will include an initial 4
weeks without use of inhaled tobramycin or other inhaled antibiotics, followed by a 4-week
period with inhaled tobramycin use. All subjects participating in the extension phase of the
study will be provided azithromycin 500mg tablets to be taken thrice weekly for the entire
8-week period.

This study will investigate how use of chronic oral azithromycin affects some of the
previously demonstrated benefits to health when using inhaled tobramycin. The primary
measurements will focus on lung function. Additional measurements will focus on
disease-related quality of life as reported by subjects in the trial. Exploratory outcomes,
including measurements of safety, are also planned.

Inclusion Criteria:

- 12 years old or older

- documented diagnosis of cystic fibrosis

- written informed consent (and assent when applicable)

- at least two respiratory cultures growing P. aeruginosa within the last 12 months

- FEV1% predicted between 25-100%

- use of at least two cycles of inhaled tobramycin within the last 24 weeks

- Off TISP and other inhaled anti-pseudomonal antibiotics for at least 2 weeks at Visit
1 and remain off of any inhaled antibiotics for an additional 2 weeks before starting
inhaled tobramycin

- most recent liver function test results less than 4 times the upper limit of normal,
obtained within the last 12 months

- prior or current use of azithromycin for at least four consecutive weeks

- stable clinical status and therapeutic regimen

Exclusion Criteria:

- weight <40 kg

- positive pregnancy test, lactating, or unwillingness to practice a pre-defined form of
contraception, which includes abstinence

- inability to perform reproducible spirometry

- inability or unwillingness to cycle off of inhaled tobramycin for one 4-week period
and without use of any additional inhaled antibiotics

- respiratory culture with Burkholderia cepacia complex species within 24 months or with
nontuberculous mycobacteria within 18 months of screening

- use of intravenous or oral anti-pseudomonal antibiotics within 4 weeks of screening

- use of investigational therapy within 4 weeks of screening

- use of systemic corticosteroids equivalent to a daily dose more than 10mg of
prednisone

- use of nelfinavir, warfarin, haloperidol, or methadone (concern of drug interaction
with azithromycin)

- initiation of CFTR modulator therapy within 30 days

- ECG abnormality at screening requiring prompt further medical attention, or QTc
interval >480 msec for males and >486 msec for females

- any other condition that, in the opinion of the site investigator, would compromise
the safety of the subject or quality of the data