Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: azithromycin; placebo (for azithromycin); inhaled tobramycin
Intervention description: 500mg tablet over-encapsulated to match placebo; clinically prescribed inhaled tobramycin used by subjects participating in the study
Intervention MeSH terms: Azithromycin; Tobramycin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 119.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      This is a study to examine the effect of combining chronic oral azithromycin with inhaled
      tobramycin in adolescent and adult subjects with cystic fibrosis who are chronically infected
      with P. aeruginosa.
    

Eligibility criteria:

        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