Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)

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 cystic fibrosis transmembrane conductance regulator (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