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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00645788




Registration number
NCT00645788
Ethics application status
Date submitted
26/03/2008
Date registered
28/03/2008
Date last updated
9/06/2014

Titles & IDs
Public title
Study to Evaluate the Safety and Efficacy of Ciprofloxacin (Inhaled) in Patients With Cystic Fibrosis
Scientific 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
Secondary ID [1] 0 0
2008-008314-40
Secondary ID [2] 0 0
12429
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ciprofloxacin (Cipro Inhale, BAYQ3939)
Treatment: Drugs - Placebo
Treatment: Drugs - Ciprofloxacin (Cipro Inhale, BAYQ3939)
Treatment: Drugs - Placebo

Experimental: 32.50 mg Ciprofloxacin DPI (BAYQ3939) - 32.50 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days

Experimental: 48.75 mg Ciprofloxacin DPI (BAYQ3939) - 48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days

Placebo Comparator: Matching Placebo for 32.50 mg - Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days

Placebo Comparator: Matching Placebo for 48.75 mg - Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days


Treatment: Drugs: Ciprofloxacin (Cipro Inhale, BAYQ3939)
32.5 mg ciprofloxacin DPI corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation powder twice a day for 28 days

Treatment: Drugs: Placebo
50 mg matching placebo powder formulation twice a day for 28 days

Treatment: Drugs: Ciprofloxacin (Cipro Inhale, BAYQ3939)
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)

Treatment: Drugs: Placebo
75 mg matching placebo powder formulation twice a day for 28 days (Arm 3 and Arm 4 was introduced after amendment 2)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28-30 - FEV1: The maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters at body temperature and ambient pressure saturated with water vapor (BTPS). This was recorded at the site using a spirometer. The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
Timepoint [1] 0 0
Baseline and End of treatment (Day 28-30)
Secondary outcome [1] 0 0
Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 - FEV1: The maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters at body temperature and ambient pressure saturated with water vapor (BTPS). This was recorded at the site using a spirometer. The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
Timepoint [1] 0 0
Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60).
Secondary outcome [2] 0 0
Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 - Density of P. aeruginosa in the sputum is expressed as log10 of colony forming units (CFU)/gram (g). The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
Timepoint [2] 0 0
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).
Secondary outcome [3] 0 0
Time to First Pulmonary Exacerbation Requiring Intervention - Pulmonary exacerbations: Assessment of pulmonary exacerbation was conducted by the treating physician as part of the physical examination. Pulmonary exacerbation was defined by chest examination findings and any or all of the following symptoms: decreased exercise tolerance, increased cough, increased sputum/cough congestion, school or work absenteeism, increased adventitial sounds on the lung examination, and decreased appetite.
Timepoint [3] 0 0
Up to visit 9 (Day 56-60)
Secondary outcome [4] 0 0
Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 - FVC: The maximal volume of air exhaled with maximally forced effort from a maximal inspiration, ie, vital capacity performed with a maximally forced expiratory effort expressed in liters at BTPS (body temperature and ambient pressure saturated with water vapor). The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
Timepoint [4] 0 0
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).
Secondary outcome [5] 0 0
Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 - FEF 25-75% (also known as the maximum midexpiratory flow [MMEF]): The mean forced expiration flow over the middle half of the forced vital capacity (FVC). It was taken from the blow with the largest sum of FEV1 and FVC. The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
Timepoint [5] 0 0
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).
Secondary outcome [6] 0 0
Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates - Susceptibility and resistance assessment of a bacterial isolate was performed using the established Food and Drug Administration (FDA) susceptibility criteria for ciprofloxacin. The susceptibility criteria in mg/L are =1 for organisms Enterobacteriaciae, P. aeruginosa, Staphylococcus species and S. pneumoniae. The "susceptible" bacterial species likely responds to typical doses of ciprofloxacin. The resistance criteria for ciprofloxacin in mg/L are =4 mg/L for the same organisms. Resistance indicates that the bacteria is less likely to respond to typical doses of ciprofloxacin therapy.
Timepoint [6] 0 0
Baseline and up to visit 9 (day 56-60)
Secondary outcome [7] 0 0
Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates - Susceptibility and resistance assessment of a bacterial isolate was performed using the established Food and Drug Administration (FDA) susceptibility criteria for ciprofloxacin. The susceptibility criteria in mg/L are =1 for organisms Enterobacteriaciae, P. aeruginosa, Staphylococcus species and S. pneumoniae. The "susceptible" bacterial species likely responds to typical doses of ciprofloxacin. The resistance criteria for ciprofloxacin in mg/L are =4 mg/L for the same organisms. Resistance indicates that the bacteria is less likely to respond to typical doses of ciprofloxacin therapy.
Timepoint [7] 0 0
Baseline and up to visit 9 (day 56-60)
Secondary outcome [8] 0 0
Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale - The CF quality of life questionnaire revised (CFQ-R), a validated disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents and adults with cystic fibrosis (CF). It is self-administered and consists of 44 items, divided into 12 generic and disease-specific scales. The scale includes physical functioning, role, vitality, emotional functioning, social functioning, body image, eating disturbances, treatment burden, health perceptions, weight, respiratory symptoms, and digestive symptoms. Scale range: 0 to 100 (maximum). Better outcome with higher values.
Timepoint [8] 0 0
Baseline and Visit 7 (Day 28-30) and Visit 9 (Day 56 -60)
Secondary outcome [9] 0 0
Plasma Concentrations of Ciprofloxacin From Selected Participants During Treatment - Plasma concentrations measured using validated high pressure liquid chromatography-mass specroscopy/mass spectroscopy (HPLC-MS/MS) methods in selected patients at predefined time windows to contribute pharmacokinetic (PK) information for an inter-study population PK evaluation. Sampling window for Plasma: Predose (trough level), <15 min, 2.0 - 2.5 hour, and 4.0 - 7.0 hours after the end of inhalation. Number of samples vary at different time points.
Timepoint [9] 0 0
Up to visit 7 (Day 28-30)
Secondary outcome [10] 0 0
Sputum Concentrations of Ciprofloxacin From Selected Participants During Treatment - Sputum concentrations measured using validated HPLC-MS/MS methods in selected patients to contribute kinetic information for an inter-study population sputum kinetic evaluation. Number of samples vary at different time points.
Timepoint [10] 0 0
Up to visit 7 (Day 28-30)
Secondary outcome [11] 0 0
Number of Participants With the Occurrence of Drug Induced Bronchospasms - Bronchospasm reported as adverse event: Bronchospasm defined as >=15% drop in FEV1, and may also include allergic and excercise-induced bronchospasm. Drug-induced bronchospasm: Treatment-emergent bronchospasm was defined as >=15% drop in FEV1 in the ITT/safety population. Note: One of the bronchospasm events was considered a serious adverse event, and it was not included under "other" adverse events. A sum of bronchospasm events was 1+6=7.
Timepoint [11] 0 0
Up to visit 9 (Day 56-60)

Eligibility
Key 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 ?F508 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
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
- Brisbane
Recruitment hospital [2] 0 0
- Chermside
Recruitment hospital [3] 0 0
- South Brisbane
Recruitment hospital [4] 0 0
- Adelaide
Recruitment hospital [5] 0 0
- Clayton
Recruitment hospital [6] 0 0
- Parkville
Recruitment hospital [7] 0 0
- Nedlands
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3052 - Parkville
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Iowa
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Mississippi
Country [15] 0 0
United States of America
State/province [15] 0 0
Nevada
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Oklahoma
Country [21] 0 0
United States of America
State/province [21] 0 0
Pennsylvania
Country [22] 0 0
United States of America
State/province [22] 0 0
South Carolina
Country [23] 0 0
United States of America
State/province [23] 0 0
Tennessee
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Utah
Country [26] 0 0
United States of America
State/province [26] 0 0
Virginia
Country [27] 0 0
United States of America
State/province [27] 0 0
Washington
Country [28] 0 0
United States of America
State/province [28] 0 0
Wisconsin
Country [29] 0 0
Canada
State/province [29] 0 0
Newfoundland and Labrador
Country [30] 0 0
Canada
State/province [30] 0 0
Ontario
Country [31] 0 0
Canada
State/province [31] 0 0
Quebec
Country [32] 0 0
Denmark
State/province [32] 0 0
Copenhagen
Country [33] 0 0
Germany
State/province [33] 0 0
Bayern
Country [34] 0 0
Germany
State/province [34] 0 0
Hessen
Country [35] 0 0
Germany
State/province [35] 0 0
Sachsen
Country [36] 0 0
Germany
State/province [36] 0 0
Berlin
Country [37] 0 0
Israel
State/province [37] 0 0
Haifa
Country [38] 0 0
Israel
State/province [38] 0 0
Jerusalem
Country [39] 0 0
Israel
State/province [39] 0 0
Petach Tikva
Country [40] 0 0
Israel
State/province [40] 0 0
Tel Hashomer
Country [41] 0 0
Norway
State/province [41] 0 0
Oslo
Country [42] 0 0
Sweden
State/province [42] 0 0
Göteborg
Country [43] 0 0
Sweden
State/province [43] 0 0
Lund
Country [44] 0 0
Sweden
State/province [44] 0 0
Uppsala
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Cambridgeshire
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Hampshire
Country [47] 0 0
United Kingdom
State/province [47] 0 0
North Ireland
Country [48] 0 0
United Kingdom
State/province [48] 0 0
West Midlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novartis
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00645788
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications