Study to Evaluate the Safety and Efficacy of Ciprofloxacin (Inhaled) in Patients With Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: Ciprofloxacin (Cipro Inhale, BAYQ3939); Placebo; Ciprofloxacin (Cipro Inhale, BAYQ3939); Placebo
Intervention description: 32.5 mg ciprofloxacin DPI corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation powder twice a day for 28 days; 50 mg matching placebo powder formulation twice a day for 28 days; 48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation powder twice a day for 28 days (Arm 3 and Arm 4 was introduced after amendment 2); 75 mg matching placebo powder formulation twice a day for 28 days (Arm 3 and Arm 4 was introduced after amendment 2)
Intervention MeSH terms: Ciprofloxacin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 288.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Ciprofloxacin; cystic fibrosis; sweat test; pulmonary function test

Summary:

      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.
    

Eligibility criteria:

        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