Study to Evaluate the Safety and Efficacy of Ciprofloxacin (Inhaled) in Patients With Cystic Fibrosis

Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of Inhaled Ciprofloxacin Compared to Placebo in Subjects With Cystic Fibrosis

To evaluate the change in forced expiratory volume (FEV1) from baseline to Day 28-30 between Cipro Inhale-treated and placebo-treated subjects after a 4-week treatment period.

Safety issues are addressed in the Adverse Events section.

Inclusion Criteria:

• Subjects, or their legal representative(s), must have given their written informed consent to participate in the study after receiving adequate previous information and prior to any study specific procedures

• Children (12 - 17 years) or adults >/=18 years

• Documented diagnosis Cystic Fibrosis (CF):

  • documented sweat chloride >/=60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) or nasal potential difference
  • either homozygous for ΔF508 genetic mutation or a compound heterozygous for 2 known CF mutations
  • and clinical findings consistent with CF

• Chronic colonization with P. aeruginosa defined as a positive respiratory tract culture (sputum or throat swab) within 12 months prior to screening and at screening (Note: subjects with negative culture at screening can, at the discretion of the investigator, be rescreened at a later date)

• Ability to perform reproducible pulmonary function tests

• Ability to produce sputum (noninduced)

• Stable pulmonary status, FEV1 >/=35% to </=75% (intraindividual variability +/-10% of absolute value). Note: The subject is not eligible for enrollment if the variability results in (or leads to) an FEV1 <35%.

• Room air oximetry >/=88% saturation

• Off antibiotics (except macrolide) and Cipro (oral) for at least 30 days prior to the administration of study drug for pulmonary exacerbation

• Stable regimen of standard CF treatment including chest physiotherapies and exercise regimens should not change during the 30 days prior to the administration of study drug and during the study (including macrolide administration unchanged in the previous 30 days)

• Subjects who are able to understand and follow instructions and who are able to participate in the study for the entire period

• Women who are willing to use an adequate method of contraception for 3 months after receiving the study drug. Adequate methods of contraception include vasectomy or condom use by their partners, diaphragm with spermicidal gel, coil (intrauterine device), surgical sterilization or oral contraceptive

Exclusion Criteria:

• Findings on screening history and physical examination unrelated to CF that could potentially affect the efficacy measurements (eg, chest surgery)
• Subjects with colonization of Pseudomonas aeruginosa and a CIPRO MIC of >/=256 µg/ml or mg/l
• Burkholderia cepacia complex colonization of their respiratory tract within the past 12 months (documented by screen laboratory)
• Known aspergillosis (unless asymptomatic). Patients with invasive disease, ABPA with IGE > 500 mg/dL will be excluded
• Transaminase level >3x upper limit of normal (ULN)
• Massive hemoptysis (>/=300 cc or requiring blood transfusion) in the preceding 4 weeks
• Intravenous antibiotic treatment for pulmonary exacerbation in the past 30 days
• Subjects with a medical disorder, condition or history of such that would impair the subject's ability to participate or complete this study in the opinion of the investigator or the sponsor
• Febrile illness within 1 week before the start of the study
• Active treatment for nontuberculosis mycobacteria
• Exposure to any investigational drug within 30 days
• Any history of allergic reaction to fluoroquinolones or other quinolones
• On oral steroids >20 mg/day for longer than 14 days in the past 3 months
• Creatinine >/=2x ULN