Official Title: “Multi-Center, Multi-National, Randomized, Placebo-Controlled Trial of Azithromycin in Subjects With Cystic Fibrosis 6-18 Years Old, Culture Negative for Pseudomonas Aeruginosa”

This is a study to examine the safety, effect on lung function, and frequency of symptoms relating to cystic fibrosis during 24 weeks of treatment with the antibiotic azithromycin in 6-18 year-olds with CF who are not infected with Pseudomonas aeruginosa.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2009

Azithromycin is an antibiotic that has been shown to improve lung function in patients with cystic fibrosis (CF) whose lungs are infected with a bacterium called Pseudomonas aeruginosa.

Scientists are not sure how azithromycin works in cystic fibrosis. It does not appear to work by killing the bacteria Pseudomonas aeruginosa, but it may make these bacteria and other bacteria less damaging to the lungs by reducing their ability to attach to the lining of the lung, or by reducing the bacteria's ability to make substances that damage the lungs of patients with cystic fibrosis. Azithromycin may also work directly on the cells in the lungs to improve lung function. This could occur by reducing inflammation (swelling) in the lungs, and/or making the mucus less sticky, or by affecting the salt channel that doesn't function correctly in CF. If azithromycin works in one or more of these ways; it may also be effective in improving lung function in cystic fibrosis patients who are not infected with Pseudomonas aeruginosa.

We are conducting this research study to examine the safety, effect on lung function and frequency of symptoms relating to cystic fibrosis during 24 weeks of treatment with the antibiotic azithromycin. This study is designed to determine if patients with cystic fibrosis whose lungs are not infected with the bacteria Pseudomonas aeruginosa will benefit from 24 weeks of treatment with the antibiotic azithromycin. Benefit will be determined as having better pulmonary function tests and getting sick less often compared to a placebo (sugar pill). This study is also designed to determine if azithromycin is safe when administered for 24 weeks to cystic fibrosis patients not infected with Pseudomonas aeruginosa. By doing this study, we hope to learn more about CF and improve the way in which we treat it.

Comparison: Three times weekly azithromycin tablets added to standard care, compared to three times weekly placebo tablets added to standard care.

Intervention(s) in this Clinical Trial

• Drug: azithromycin 250 mg tablets
  • One (1) tablet three times weekly for patients who weigh 40-79 lbs Two (2) tablets three times weekly for patients who weigh greater than or equal to 80 lbs
• Drug: placebo tablets
  • One (1) tablet three times weekly for patients who weigh 40-79 lbs Two (2) tablets three times weekly for patients who weigh greater than or equal to 80 lbs

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • azithromycin tablets
• Placebo Comparator: 2
  • placebo tablets (matched to active drug in appearance)

Primary Measures

• Change in FEV1 from baseline to end of treatment
  • Time Frame: 24 weeks
    Safety Issue?: Yes

Secondary Measures

• Safety, frequency of pulmonary exacerbations, changes in other measures of lung function, treatment emergent pathogens, weight, and serum inflammatory markers
  • Time Frame: 24 weeks
    Safety Issue?: Yes

Inclusion Criteria:

• Male or female, 6-18 years of age at enrollment
• Confirmed diagnosis of CF
• Written informed consent (and assent when applicable)
• Clinically stable at enrollment as assessed by the site investigator
• FEV1 % predicted > 50%
• Ability to comply with medication use, study visits, and study procedures
• Ability to swallow a 250 mg tablet

Exclusion Criteria:

• Weight less than 18.0 kg
• Respiratory culture positive for P. aeruginosa, NTM, or B. cepacia complex within 1 year or at screening, or AFB positive at screening
• Allergy to macrolide antibiotics
• Use of macrolide antibiotics (e.g., azithromycin, clarithromycin) within 60 days of screening
• Use of systemic corticosteroids or intravenous or oral antibiotics within 14 days of screening
• Initiation of high dose ibuprofen, Pulmozyme®, hypertonic saline or aerosolized antibiotics within 30 days of screening
• Chronic therapy with drugs known to have rare but serious interactions with azithromycin: amiodarone, digoxin, disopyramide, lovastatin, pimozide, rifabutin, and nelfinavir
• Investigational drug use within 30 days of screening
• Laboratory abnormalities (creatinine, liver function or neutropenia) at screening and confirmed at follow-up testing prior to randomization
• History of biliary cirrhosis, portal hypertension, or splenomegaly, or splenomegaly on physical exam
• History of ventricular arrhythmia
• Other major organ dysfunction, excluding pancreatic dysfunction
• History of lung transplantation or currently on lung transplant list
• Relative decrease in FEV1 % predicted ≥ 20% between the screening and enrollment visit
• Positive serum pregnancy test at screening
• Pregnant, breastfeeding, or if post-menarche female, unwilling to practice birth control during participation in the study
• History of alcohol, illicit drug or medication abuse within 1 year of screening in the judgment of the site investigator
• Presence of a condition or abnormality that in the opinion of the site investigator would compromise the safety of the subject or the quality of the data

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 6 Years

Maximum Age for this Clinical Trial: 18 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: CF Therapeutics Development Network Coordinating Center

Overall Clinical Trial Officials and Contacts

Lisa Saiman, MD, MPH Principal Investigator Columbia University  

Overall Contact: Jasna Hocevar-Trnka, MPH 206-884-7527 jasna.hocevar-trnka@seattlechildrens.org

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00431964

Study ID Number: AZ0004

ClinicalTrials.gov Identifier: NCT00431964

Health Authority: United States: Food and Drug Administration