Clinical trial NCT00645788: Study to Evaluate the Safety and Efficacy of Ciprofloxacin (Inhaled) in Patients With Cystic Fibrosis
Official title: Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of Inhaled Ciprofloxacin Compared to Placebo in Subjects With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Ciprofloxacin
cystic fibrosis
sweat test
pulmonary function test
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Novartis
First posted: 2008-03-28
Enrollment: 288
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Safety issues are addressed in the Adverse Events section.

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

Primary outcomes:
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28-30
timeFrame: Baseline and End of treatment (Day 28-30)
Secondary outcomes:
measure: Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9
timeFrame: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60).
measure: Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9
timeFrame: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 7 (Day 28-30), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60).
measure: Time to First Pulmonary Exacerbation Requiring Intervention
timeFrame: Up to visit 9 (Day 56-60)
measure: Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9
timeFrame: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 7 (Day 28-30), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60).
measure: Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9
timeFrame: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 7 (Day 28-30), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60).
measure: Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates
timeFrame: Baseline and up to visit 9 (day 56-60)
measure: Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates
timeFrame: Baseline and up to visit 9 (day 56-60)
measure: Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale
timeFrame: Baseline and Visit 7 (Day 28-30) and Visit 9 (Day 56 -60)
measure: Plasma Concentrations of Ciprofloxacin From Selected Participants During Treatment
timeFrame: Up to visit 7 (Day 28-30)
measure: Sputum Concentrations of Ciprofloxacin From Selected Participants During Treatment
timeFrame: Up to visit 7 (Day 28-30)
measure: Number of Participants With the Occurrence of Drug Induced Bronchospasms
timeFrame: Up to visit 9 (Day 56-60)
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Orange
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Ventura
country: United States
state: California
city: Aurora
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state: Colorado
city: Hartford
country: United States
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Glenview
country: United States
state: Illinois
city: Maywood
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Iowa city
country: United States
state: Iowa
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Kalamazoo
country: United States
state: Michigan
city: Jackson
country: United States
state: Mississippi
city: Las Vegas
country: United States
state: Nevada
city: Livingston
country: United States
state: New Jersey
city: Long Branch
country: United States
state: New Jersey
city: Morristown
country: United States
state: New Jersey
city: Somerville
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: New Hyde Park
country: United States
state: New York
city: Valhalla
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Hershey
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Knoxville
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Charlottesville
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Brisbane
country: Australia
state: Queensland
city: Chermside
country: Australia
state: Queensland
city: South Brisbane
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Clayton
country: Australia
state: Victoria
city: Parkville
country: Australia
state: Victoria
city: Nedlands
country: Australia
state: Western Australia
city: St. John's
country: Canada
state: Newfoundland and Labrador
city: Hamilton
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Copenhagen
country: Denmark
city: München
country: Germany
state: Bayern
city: Frankfurt
country: Germany
state: Hessen
city: Leipzig
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petach Tikva
country: Israel
city: Tel Hashomer
country: Israel
city: Oslo
country: Norway
city: Göteborg
country: Sweden
city: Lund
country: Sweden
city: Uppsala
country: Sweden
city: Cambridge
country: United Kingdom
state: Cambridgeshire
city: Southampton
country: United Kingdom
state: Hampshire
city: Belfast
country: United Kingdom
state: North Ireland
city: Birmingham
country: United Kingdom
state: West Midlands
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Dorkin HL, Staab D, Operschall E, Alder J, Criollo M. Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis. BMJ Open Respir Res. 2015 Dec 2;2(1):e000100. doi: 10.1136/bmjresp-2015-000100. eCollection 2015.