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

Bayer

Status and phase: Completed; Phase 2

Conditions: Cystic Fibrosis

Treatments: Drug: Ciprofloxacin (Cipro Inhale, BAYQ3939); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00645788

2008-008314-40 (EudraCT Number)

12429

Details and patient eligibility

About

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.

Full description

Safety issues are addressed in the Adverse Events section.

Enrollment: 288 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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288 participants in 4 patient groups, including a placebo group

32.50 mg Ciprofloxacin DPI (BAYQ3939)

Experimental group

Description:

32.50 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days

Treatment:

Drug: Ciprofloxacin (Cipro Inhale, BAYQ3939)

Drug: Ciprofloxacin (Cipro Inhale, BAYQ3939)

48.75 mg Ciprofloxacin DPI (BAYQ3939)

Experimental group

Description:

48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days

Treatment:

Drug: Ciprofloxacin (Cipro Inhale, BAYQ3939)

Drug: Ciprofloxacin (Cipro Inhale, BAYQ3939)

Matching Placebo for 32.50 mg

Placebo Comparator group

Description:

Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days

Treatment:

Drug: Placebo

Drug: Placebo

Matching Placebo for 48.75 mg

Placebo Comparator group

Description:

Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days

Treatment:

Drug: Placebo

Drug: Placebo