Cystic Fibrosis
Conditions
Keywords
Ciprofloxacin, cystic fibrosis, sweat test, pulmonary function test
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.
Interventions
32.5 mg ciprofloxacin DPI corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation powder twice a day for 28 days
DRUGPlacebo
50 mg matching placebo powder formulation twice a day for 28 days
Sponsors
Novartis
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28-30 | Baseline and End of treatment (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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | 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). | 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. |
| Time to First Pulmonary Exacerbation Requiring Intervention | Up to visit 9 (Day 56-60) | 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. |
| Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | 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). | 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. |
| Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | 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). | 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. |
| Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates | Baseline and up to visit 9 (day 56-60) | 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. |
| Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60). | 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. |
| Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Baseline and Visit 7 (Day 28-30) and Visit 9 (Day 56 -60) | 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. |
| Plasma Concentrations of Ciprofloxacin From Selected Participants During Treatment | Up to visit 7 (Day 28-30) | 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. |
| Sputum Concentrations of Ciprofloxacin From Selected Participants During Treatment | Up to visit 7 (Day 28-30) | 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. |
| Number of Participants With the Occurrence of Drug Induced Bronchospasms | Up to visit 9 (Day 56-60) | 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. |
| Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates | Baseline and up to visit 9 (day 56-60) | 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. |
Countries
Australia, Canada, Denmark, Germany, Israel, Norway, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The first visit of the first subject was on 05 May 2008 and the last visit of the last subject on 25 Jan 2011. This study was conducted at 73 centers from 8 countries.
Pre-assignment details
Of all enrolled 486 subjects, 188 had screening failures, the remaining 288 were randomized but 2 subjects (one each in 32.5 mg Ciprofloxacin DPI (Dry Powder for Inhalation) and 48.75 mg Ciprofloxacin DPI groups) did not receive any study drug. A total of 286 subjects received one of the 4 study drug treatments.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 93 |
| 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 | 93 |
| Matching Placebo for 32.50 mg Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days | 65 |
| Matching Placebo for 48.75 mg Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days | 35 |
| Total | 286 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 9 | 5 | 3 |
| Overall Study | Did not receive study drug | 1 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 2 | 0 |
| Overall Study | Pulmonary exacerbation | 13 | 16 | 11 | 9 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | 32.50 mg Ciprofloxacin DPI (BAYQ3939) | 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Matching Placebo for 32.50 mg | Matching Placebo for 48.75 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 27.7 Years STANDARD_DEVIATION 9.3 | 29.3 Years STANDARD_DEVIATION 9.5 | 31.7 Years STANDARD_DEVIATION 12.1 | 29.1 Years STANDARD_DEVIATION 9.4 | 29.3 Years STANDARD_DEVIATION 10.1 |
| Forced expiratory volume in 1 second (FEV1) | 55.0 Percentage of predicted FEV1 STANDARD_DEVIATION 11.3 | 54.7 Percentage of predicted FEV1 STANDARD_DEVIATION 12.3 | 54.8 Percentage of predicted FEV1 STANDARD_DEVIATION 10.6 | 52.7 Percentage of predicted FEV1 STANDARD_DEVIATION 10.7 | 54.6 Percentage of predicted FEV1 STANDARD_DEVIATION 11.4 |
| Sex: Female, Male Female | 49 Participants | 42 Participants | 26 Participants | 16 Participants | 133 Participants |
| Sex: Female, Male Male | 44 Participants | 51 Participants | 39 Participants | 19 Participants | 153 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 67 / 93 | 74 / 93 | 45 / 65 | 25 / 35 |
| serious Total, serious adverse events | 7 / 93 | 17 / 93 | 7 / 65 | 3 / 35 |
Outcome results
Primary
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.
Time frame: Baseline and End of treatment (Day 28-30)
Population: Intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28-30 | -1.0 Percent of predicted FEV1 | Standard Deviation 6.01 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28-30 | -0.62 Percent of predicted FEV1 | Standard Deviation 5.52 |
| Matching Placebo for 32.50 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28-30 | -2.2 Percent of predicted FEV1 | Standard Deviation 5.47 |
| Matching Placebo for 48.75 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28-30 | -2.2 Percent of predicted FEV1 | Standard Deviation 5.17 |
Comparison: Ho: \|Cipro 32.5 mg - matching placebo\|=0 and \|Cipro 48.75 mg - matching placebo\|=0p-value: 0.076ANCOVA
Secondary
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.
Time frame: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60).
Population: Intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 4 | 0.40 Percent of predicted FEV1 | Standard Deviation 5.14 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 5 | 0.10 Percent of predicted FEV1 | Standard Deviation 6.14 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 8 | -1.5 Percent of predicted FEV1 | Standard Deviation 5.95 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 9 | -2.0 Percent of predicted FEV1 | Standard Deviation 5.22 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 5 | 0.26 Percent of predicted FEV1 | Standard Deviation 3.94 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 8 | -0.71 Percent of predicted FEV1 | Standard Deviation 5.14 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 9 | -0.95 Percent of predicted FEV1 | Standard Deviation 5.29 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 4 | 0.65 Percent of predicted FEV1 | Standard Deviation 4.62 |
| Matching Placebo for 32.50 mg | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 8 | -1.2 Percent of predicted FEV1 | Standard Deviation 6.04 |
| Matching Placebo for 32.50 mg | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 5 | -1.6 Percent of predicted FEV1 | Standard Deviation 3.59 |
| Matching Placebo for 32.50 mg | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 9 | -1.9 Percent of predicted FEV1 | Standard Deviation 4.89 |
| Matching Placebo for 32.50 mg | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 4 | -0.84 Percent of predicted FEV1 | Standard Deviation 3.92 |
| Matching Placebo for 48.75 mg | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 9 | -1.6 Percent of predicted FEV1 | Standard Deviation 5.13 |
| Matching Placebo for 48.75 mg | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 5 | -0.87 Percent of predicted FEV1 | Standard Deviation 4 |
| Matching Placebo for 48.75 mg | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 4 | -0.36 Percent of predicted FEV1 | Standard Deviation 3.5 |
| Matching Placebo for 48.75 mg | Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 | Visit 8 | -1.6 Percent of predicted FEV1 | Standard Deviation 5.23 |
Secondary
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.
Time frame: 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).
Population: Intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 7 | 0.24 Percent of predicted FEF 25-75% | Standard Deviation 6.84 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 8 | 0.16 Percent of predicted FEF 25-75% | Standard Deviation 7.56 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 4 | 2.13 Percent of predicted FEF 25-75% | Standard Deviation 7.12 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 5 | 1.48 Percent of predicted FEF 25-75% | Standard Deviation 8.16 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 9 | -0.46 Percent of predicted FEF 25-75% | Standard Deviation 7.35 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 7 | 0.35 Percent of predicted FEF 25-75% | Standard Deviation 5.39 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 8 | -0.33 Percent of predicted FEF 25-75% | Standard Deviation 5.19 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 5 | 0.95 Percent of predicted FEF 25-75% | Standard Deviation 4.73 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 4 | 1.09 Percent of predicted FEF 25-75% | Standard Deviation 6.9 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 9 | -0.49 Percent of predicted FEF 25-75% | Standard Deviation 5.55 |
| Matching Placebo for 32.50 mg | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 7 | -2.1 Percent of predicted FEF 25-75% | Standard Deviation 5.62 |
| Matching Placebo for 32.50 mg | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 4 | -1.0 Percent of predicted FEF 25-75% | Standard Deviation 4.65 |
| Matching Placebo for 32.50 mg | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 5 | -1.1 Percent of predicted FEF 25-75% | Standard Deviation 4.49 |
| Matching Placebo for 32.50 mg | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 8 | -1.2 Percent of predicted FEF 25-75% | Standard Deviation 6.23 |
| Matching Placebo for 32.50 mg | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 9 | -1.3 Percent of predicted FEF 25-75% | Standard Deviation 5.63 |
| Matching Placebo for 48.75 mg | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 8 | -1.9 Percent of predicted FEF 25-75% | Standard Deviation 5.31 |
| Matching Placebo for 48.75 mg | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 5 | -0.89 Percent of predicted FEF 25-75% | Standard Deviation 4.16 |
| Matching Placebo for 48.75 mg | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 4 | -0.49 Percent of predicted FEF 25-75% | Standard Deviation 4.55 |
| Matching Placebo for 48.75 mg | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 7 | -1.8 Percent of predicted FEF 25-75% | Standard Deviation 4.73 |
| Matching Placebo for 48.75 mg | Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 | Visit 9 | -1.4 Percent of predicted FEF 25-75% | Standard Deviation 4.99 |
Secondary
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.
Time frame: 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).
Population: Intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 8 | -2.6 Percent of predicted FVC | Standard Deviation 8.62 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 5 | -2.2 Percent of predicted FVC | Standard Deviation 9.78 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 9 | -2.9 Percent of predicted FVC | Standard Deviation 8.54 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 7 | -2.8 Percent of predicted FVC | Standard Deviation 8.91 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 4 | -2.5 Percent of predicted FVC | Standard Deviation 8.97 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 7 | -1.4 Percent of predicted FVC | Standard Deviation 6.04 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 8 | -0.65 Percent of predicted FVC | Standard Deviation 6.44 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 9 | -0.70 Percent of predicted FVC | Standard Deviation 6.64 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 5 | -0.48 Percent of predicted FVC | Standard Deviation 5.11 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 4 | 0.22 Percent of predicted FVC | Standard Deviation 5.07 |
| Matching Placebo for 32.50 mg | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 7 | -2.7 Percent of predicted FVC | Standard Deviation 6.97 |
| Matching Placebo for 32.50 mg | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 4 | -0.94 Percent of predicted FVC | Standard Deviation 5.23 |
| Matching Placebo for 32.50 mg | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 5 | -1.8 Percent of predicted FVC | Standard Deviation 4.51 |
| Matching Placebo for 32.50 mg | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 8 | -1.6 Percent of predicted FVC | Standard Deviation 7.31 |
| Matching Placebo for 32.50 mg | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 9 | -2.3 Percent of predicted FVC | Standard Deviation 5.63 |
| Matching Placebo for 48.75 mg | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 8 | 0.13 Percent of predicted FVC | Standard Deviation 7.72 |
| Matching Placebo for 48.75 mg | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 5 | -1.1 Percent of predicted FVC | Standard Deviation 5.57 |
| Matching Placebo for 48.75 mg | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 4 | -0.45 Percent of predicted FVC | Standard Deviation 4.98 |
| Matching Placebo for 48.75 mg | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 7 | -1.4 Percent of predicted FVC | Standard Deviation 8.41 |
| Matching Placebo for 48.75 mg | Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 | Visit 9 | -0.53 Percent of predicted FVC | Standard Deviation 7.37 |
Secondary
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.
Time frame: 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).
Population: Intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 8 | -0.26 log10(cfu/g) | Standard Deviation 2.52 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 5 | -0.98 log10(cfu/g) | Standard Deviation 2.51 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 9 | 0.13 log10(cfu/g) | Standard Deviation 2.19 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 7 | -0.73 log10(cfu/g) | Standard Deviation 2.57 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 4 | -0.76 log10(cfu/g) | Standard Deviation 2.21 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 7 | -0.78 log10(cfu/g) | Standard Deviation 2.54 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 8 | -0.11 log10(cfu/g) | Standard Deviation 2.39 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 9 | -0.16 log10(cfu/g) | Standard Deviation 2.26 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 5 | -1.0 log10(cfu/g) | Standard Deviation 2.13 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 4 | -1.1 log10(cfu/g) | Standard Deviation 1.63 |
| Matching Placebo for 32.50 mg | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 7 | -0.07 log10(cfu/g) | Standard Deviation 2.59 |
| Matching Placebo for 32.50 mg | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 4 | -0.35 log10(cfu/g) | Standard Deviation 2.09 |
| Matching Placebo for 32.50 mg | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 5 | 0.15 log10(cfu/g) | Standard Deviation 2.06 |
| Matching Placebo for 32.50 mg | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 8 | -0.14 log10(cfu/g) | Standard Deviation 2.21 |
| Matching Placebo for 32.50 mg | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 9 | -0.19 log10(cfu/g) | Standard Deviation 2.15 |
| Matching Placebo for 48.75 mg | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 8 | -0.00 log10(cfu/g) | Standard Deviation 2.43 |
| Matching Placebo for 48.75 mg | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 5 | -0.65 log10(cfu/g) | Standard Deviation 2.45 |
| Matching Placebo for 48.75 mg | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 4 | -0.56 log10(cfu/g) | Standard Deviation 2.73 |
| Matching Placebo for 48.75 mg | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 7 | -0.63 log10(cfu/g) | Standard Deviation 2.15 |
| Matching Placebo for 48.75 mg | Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 | Visit 9 | 0.54 log10(cfu/g) | Standard Deviation 1.69 |
Comparison: At visit 7 (End of treatment) Ho: \|Cipro 32.5 - matching placebo\| =0 and~\|Cipro 48.75 - matching placebo\| =0p-value: 0.068ANCOVA
Secondary
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.
Time frame: Baseline and Visit 7 (Day 28-30) and Visit 9 (Day 56 -60)
Population: Intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Baseline | 68.0 scores on a scale | Standard Deviation 18.7 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Visit 9 | 67.2 scores on a scale | Standard Deviation 18.9 |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Visit 7 | 70.8 scores on a scale | Standard Deviation 15.9 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Baseline | 59.5 scores on a scale | Standard Deviation 19 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Visit 9 | 60.6 scores on a scale | Standard Deviation 20.5 |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Visit 7 | 60.0 scores on a scale | Standard Deviation 19.7 |
| Matching Placebo for 32.50 mg | Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Visit 7 | 58.9 scores on a scale | Standard Deviation 18.7 |
| Matching Placebo for 32.50 mg | Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Baseline | 61.3 scores on a scale | Standard Deviation 18.6 |
| Matching Placebo for 32.50 mg | Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Visit 9 | 61.1 scores on a scale | Standard Deviation 19.8 |
| Matching Placebo for 48.75 mg | Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Baseline | 68.3 scores on a scale | Standard Deviation 13.8 |
| Matching Placebo for 48.75 mg | Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Visit 9 | 71.2 scores on a scale | Standard Deviation 16.6 |
| Matching Placebo for 48.75 mg | Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale | Visit 7 | 61.6 scores on a scale | Standard Deviation 18.4 |
Secondary
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.
Time frame: Baseline and up to visit 9 (day 56-60)
Population: Intent to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates | P.aeruginosa sensitive - baseline | 70 Participants |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates | P.aeruginosa resistant - up to visit 9 | 15 Participants |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates | P.aeruginosa resistant - up to visit 9 | 15 Participants |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates | P.aeruginosa sensitive - baseline | 60 Participants |
| Matching Placebo for 32.50 mg | Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates | P.aeruginosa sensitive - baseline | 51 Participants |
| Matching Placebo for 32.50 mg | Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates | P.aeruginosa resistant - up to visit 9 | 11 Participants |
| Matching Placebo for 48.75 mg | Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates | P.aeruginosa sensitive - baseline | 30 Participants |
| Matching Placebo for 48.75 mg | Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates | P.aeruginosa resistant - up to visit 9 | 3 Participants |
Secondary
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.
Time frame: Baseline and up to visit 9 (day 56-60)
Population: Intent to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates | P.aeruginosa sensitive - baseline | 72 Participants |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates | P.aeruginosa resistant- up to visit 9 | 29 Participants |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates | P.aeruginosa resistant- up to visit 9 | 31 Participants |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates | P.aeruginosa sensitive - baseline | 63 Participants |
| Matching Placebo for 32.50 mg | Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates | P.aeruginosa sensitive - baseline | 48 Participants |
| Matching Placebo for 32.50 mg | Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates | P.aeruginosa resistant- up to visit 9 | 19 Participants |
| Matching Placebo for 48.75 mg | Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates | P.aeruginosa sensitive - baseline | 23 Participants |
| Matching Placebo for 48.75 mg | Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates | P.aeruginosa resistant- up to visit 9 | 7 Participants |
Secondary
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.
Time frame: Up to visit 9 (Day 56-60)
Population: Intent to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Number of Participants With the Occurrence of Drug Induced Bronchospasms | Reported as Adverse event | 4 participants |
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Number of Participants With the Occurrence of Drug Induced Bronchospasms | Defined as >=15 percent drop in FEV1 | 3 participants |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Number of Participants With the Occurrence of Drug Induced Bronchospasms | Defined as >=15 percent drop in FEV1 | 3 participants |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Number of Participants With the Occurrence of Drug Induced Bronchospasms | Reported as Adverse event | 7 participants |
| Matching Placebo for 32.50 mg | Number of Participants With the Occurrence of Drug Induced Bronchospasms | Reported as Adverse event | 3 participants |
| Matching Placebo for 32.50 mg | Number of Participants With the Occurrence of Drug Induced Bronchospasms | Defined as >=15 percent drop in FEV1 | 3 participants |
| Matching Placebo for 48.75 mg | Number of Participants With the Occurrence of Drug Induced Bronchospasms | Reported as Adverse event | 0 participants |
| Matching Placebo for 48.75 mg | Number of Participants With the Occurrence of Drug Induced Bronchospasms | Defined as >=15 percent drop in FEV1 | 0 participants |
Secondary
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.
Time frame: Up to visit 7 (Day 28-30)
Population: Analysis was not performed due to insufficient data.
Secondary
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.
Time frame: Up to visit 7 (Day 28-30)
Population: Analysis was not performed due to insufficient data.
Secondary
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.
Time frame: Up to visit 9 (Day 56-60)
Population: Intent to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 32.50 mg Ciprofloxacin DPI (BAYQ3939) | Time to First Pulmonary Exacerbation Requiring Intervention | NA Days |
| 48.75 mg Ciprofloxacin DPI (BAYQ3939) | Time to First Pulmonary Exacerbation Requiring Intervention | NA Days |
| Matching Placebo for 32.50 mg | Time to First Pulmonary Exacerbation Requiring Intervention | NA Days |
| Matching Placebo for 48.75 mg | Time to First Pulmonary Exacerbation Requiring Intervention | NA Days |