Bronchiectasis
Conditions
Keywords
Ciprofloxacin, Airway infection, Bronchiectasis
Brief summary
The purpose of this study is to find out if bacterial load in the airways can be reduced after inhalation of ciprofloxacin for 28 days.
Detailed description
Safety issues are addressed in the AE section. There is no standardised and unanimously accepted definition of exacerbation in COPD; 4 definitions are widely used: (1) using a combination of 3 cardinal symptoms: increased dyspnea, sputum volume, and sputum purulence; (2) looking at the presence of the following patterns of symptoms during \>=2 consecutive days: either 2 or more of 3 major symptoms (increase in dyspnoea, sputum volume and sputum purulence); or any 1 major symptom together with any 1 minor symptom (increase in nasal discharge, wheeze, sore throat, cough or fever); (3) a sustained worsening of the patient's condition, from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitates a change in regular medication in a patient with underlying COPD; (4) a complex of respiratory events (i.e. cough, wheezing, dyspnoea or sputum production) lasting \>=3 days.
Interventions
Inhalation of 32,5mg Ciprofloxacin inhaled twice a day
DRUGPlacebo
Inhalation of matching placebo twice a day
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
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a proven and documented diagnosis of non-cystic fibrosis idiopathic or post pneumonic bronchiectasis * Stable pulmonary status and stable regimen of standard treatment at least for the past 30 days
Exclusion criteria
* Forced Expiratory Volume 1 \< 35% or \> 80% * Allergic bronchopulmonary aspergillosis * Immunodeficiency disease requiring immunoglobulin replacement * Inflammatory bowel disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Bacterial Load in the Sputum at End of Treatment (Day 29). | Baseline and 29 days | Total bacterial load was determined in sputum collected before the inhalation of study drug. Sputum samples were either provided by the participant during the respective study visit, or participants had to bring a sputum sample that had been produced within the 4 hours prior to the visit. Induced sputum samples could be collected if the participant was unable to produce a spontaneously expectorated sputum sample of \> 2 mL. Imputation method: last observation carried forward (LOCF). CFU: colony forming units, log10: decadic logarithm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline and up to end of study (planned at Day 84) | Pulmonary function testing (spirometry) was conducted in accordance with American Thoracic Society standards. FEV1 was defined as 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). Imputation method: last observation carried forward (LOCF). |
| Change From Baseline in Forced Vital Capacity (FVC) | Baseline and up to end of study (planned at Day 84) | Pulmonary function testing (spirometry) was conducted in accordance with American Thoracic Society standards. FVC was defined as the maximal volume of air exhaled with maximally forced effort from a maximal inspiration, i.e. vital capacity performed with a maximally forced expiratory effort expressed in liters at BTPS. Imputation method: last observation carried forward (LOCF). |
| Time to Exacerbation With Antibiotic Intervention | Up to end of study (planned at Day 84) | Acute exacerbation was defined according to the joint American Thoracic Society/European Respiratory Society criteria. For detailed information with regard to this definition of acute exacerbation, please refer to the detailed description in the protocol section. The time to an acute exacerbation with antibiotic intervention was determined. |
| Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score | Up to end of study (planned at Day 84) | Participants completed the Saint George's Respiratory Questionnaire (SGRQ). They were assured that all data would be treated confidentially and that the answers would not have any influence on study drug treatment. Participants completed the questionnaires on their own in a quiet area, without discussing them with study staff or accompanying persons (e.g. friends or relatives) and before being seen by the clinician. The score ranges from 0 to 100 with 100 being the worst possible score. |
| Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) | Up to end of study (planned at Day 84) | Participants completed the Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS). They were assured that all data would be treated confidentially and that the answers would not have any influence on study drug treatment. Participants completed the questionnaires on their own in a quiet area, without discussing them with study staff or accompanying persons (e.g. friends or relatives) and before being seen by the clinician. The score ranges between 1 and 7, 1 being the worst possible score. |
| Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | Baseline and up to Day 42 | High sensitive C-reactive protein (hsCRP) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available. |
| 24-hour Sputum Volume | Up to end of study (planned at Day 84) | Participants were asked to start 24-hour sputum collection samples 24 hours before coming for the respective study visit. The volume of the completed sample was determined. |
| 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Up to end of study (planned at Day 84) | Participants were asked to start 24-hour sputum collection samples 24 hours before coming for the respective study visit. Sputum color was assessed as either 'clear', or as 'yellow', 'green' or 'rust', or an assessment of 'no sputum' was made. |
| Microbiological Response of Cipro Inhale Per Participant | Up to end of study (planned at Day 84) | Microbiological response was defined as reduction in bacterial load or eradication (measured as the percentage of participants with positive culture). Missing values were not imputed. |
| Microbiological Response of Cipro Inhale Per Pathogen | Up to end of study (planned at Day 84) | Microbiological response was defined as reduction in bacterial load or eradication (measured as the number of participants with positive culture). Missing values were not imputed. Pathogens analyzed: Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Serratia marcescens, Pseudomonas aeruginosa, mucoid, Pseudomonas aeruginosa, non mucoid, Stenotrophomonas maltophilia, Achromobacter xylosoxydans, Moraxella catarrhalis, Haemophilus influenzae |
| Emergence of New Potential Respiratory Pathogens | Up to end of study (planned at Day 84) | The emergence of new potential respiratory pathogens was evaluated using microbiological analysis. Evaluated was the cumulative number of participants with first appearance of new potential respiratory antigens at each time point. In some cases, participants attended the end of study visit later than Day 84 (up to Day 88). |
| Emergence of Resistance Among Baseline Pathogens | Up to end of study (planned at Day 84) | The emergence of resistance (at least two-fold increase of Minimal inhibitory concentration, MIC, vs. baseline values) probably or possibly related to study medication among baseline pathogens was evaluated using microbiological analysis. |
| Change From Baseline in Absolute Neutrophil Count (ANC) | Baseline and up to Day 42 | Absolute neutrophil count (ANC) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Bacterial Load in the Sputum | Baseline and up to end of study (planned at Day 84) | Total bacterial load was determined in sputum collected before the inhalation of study drug. Sputum samples were either provided by the participant during the respective study visit, or participants had to bring a sputum sample that had been produced within the 4 hours prior to the visit. Induced sputum samples could be collected if the participant was unable to produce a spontaneously expectorated sputum sample of \> 2 mL on Day 8. Imputation method: last observation carried forward (LOCF). CFU: colony forming units, log10: decadic logarithm |
Countries
Australia, Germany, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
Pulmonary stable participants with a proven and documented diagnosis of non-cystic fibrosis bronchiectasis (idiopathic or postpneumonic), and on a stable regimen of standard treatment, were recruited at specialized study sites.
Pre-assignment details
Out of 277 participants screened, 153 failed screening (mostly due to not meeting in-/exclusion criteria or inability to produce adequate sputum samples), and 124 participants were randomized (60 to Ciprofloxacin Inhale and 64 to placebo).
Participants by arm
| Arm | Count |
|---|---|
| Ciprofloxacin Inhale (BAYQ3939) 32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily | 60 |
| Placebo Inhalation of matching placebo twice a day | 64 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 19 | 23 |
| Overall Study | Protocol Violation | 1 | 5 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Ciprofloxacin Inhale (BAYQ3939) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 64.7 Years STANDARD_DEVIATION 11.8 | 61.4 Years STANDARD_DEVIATION 11.9 | 63.0 Years STANDARD_DEVIATION 11.9 |
| Sex: Female, Male Female | 39 Participants | 43 Participants | 82 Participants |
| Sex: Female, Male Male | 21 Participants | 21 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 60 | 36 / 64 |
| serious Total, serious adverse events | 4 / 60 | 6 / 64 |
Outcome results
Primary
Change From Baseline in Total Bacterial Load in the Sputum at End of Treatment (Day 29).
Total bacterial load was determined in sputum collected before the inhalation of study drug. Sputum samples were either provided by the participant during the respective study visit, or participants had to bring a sputum sample that had been produced within the 4 hours prior to the visit. Induced sputum samples could be collected if the participant was unable to produce a spontaneously expectorated sputum sample of \> 2 mL. Imputation method: last observation carried forward (LOCF). CFU: colony forming units, log10: decadic logarithm
Time frame: Baseline and 29 days
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Total Bacterial Load in the Sputum at End of Treatment (Day 29). | -2.94 log10 of CFU per gram sputum | Standard Deviation 3.4 |
| Placebo | Change From Baseline in Total Bacterial Load in the Sputum at End of Treatment (Day 29). | -0.32 log10 of CFU per gram sputum | Standard Deviation 2.29 |
Comparison: Ho: CFU(EOT\|Cipro) - CFU(baseline\|Cipro) \> CFU(EOT\|Placebo) - CFU(baseline\|Placebo) CFU = colony forming units EOT=End of treatment (Day 29) Sample size was based a difference of 1.2 log10 CFU/g between placebo and Ciprofloxacin and a standard deviation of 2 log10 CFU/gp-value: <0.001ANCOVA
Secondary
24-hour Sputum Color (Percentage of Participants With Non-clear Sputum)
Participants were asked to start 24-hour sputum collection samples 24 hours before coming for the respective study visit. Sputum color was assessed as either 'clear', or as 'yellow', 'green' or 'rust', or an assessment of 'no sputum' was made.
Time frame: Up to end of study (planned at Day 84)
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Day 1 | 91.7 Percentage of participants |
| Ciprofloxacin Inhale (BAYQ3939) | 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Day 8 | 73.2 Percentage of participants |
| Ciprofloxacin Inhale (BAYQ3939) | 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Day 29 | 75.5 Percentage of participants |
| Ciprofloxacin Inhale (BAYQ3939) | 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Day 42 | 72.8 Percentage of participants |
| Ciprofloxacin Inhale (BAYQ3939) | 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Day 56 | 75.0 Percentage of participants |
| Ciprofloxacin Inhale (BAYQ3939) | 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Day 84 | 66.6 Percentage of participants |
| Placebo | 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Day 56 | 86.5 Percentage of participants |
| Placebo | 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Day 1 | 88.9 Percentage of participants |
| Placebo | 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Day 42 | 88.4 Percentage of participants |
| Placebo | 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Day 8 | 94.9 Percentage of participants |
| Placebo | 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Day 84 | 72.8 Percentage of participants |
| Placebo | 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Day 29 | 82.7 Percentage of participants |
Secondary
24-hour Sputum Volume
Participants were asked to start 24-hour sputum collection samples 24 hours before coming for the respective study visit. The volume of the completed sample was determined.
Time frame: Up to end of study (planned at Day 84)
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | 24-hour Sputum Volume | Day 1 | 24.9 mL | Standard Deviation 23.6 |
| Ciprofloxacin Inhale (BAYQ3939) | 24-hour Sputum Volume | Day 8 | 18.9 mL | Standard Deviation 22.2 |
| Ciprofloxacin Inhale (BAYQ3939) | 24-hour Sputum Volume | Day 29 | 20.5 mL | Standard Deviation 25.3 |
| Ciprofloxacin Inhale (BAYQ3939) | 24-hour Sputum Volume | Day 42 | 21.1 mL | Standard Deviation 24.7 |
| Ciprofloxacin Inhale (BAYQ3939) | 24-hour Sputum Volume | Day 56 | 19.6 mL | Standard Deviation 24.8 |
| Ciprofloxacin Inhale (BAYQ3939) | 24-hour Sputum Volume | Day 84 | 23.6 mL | Standard Deviation 28.9 |
| Placebo | 24-hour Sputum Volume | Day 56 | 22.0 mL | Standard Deviation 24.8 |
| Placebo | 24-hour Sputum Volume | Day 1 | 30.2 mL | Standard Deviation 25.2 |
| Placebo | 24-hour Sputum Volume | Day 42 | 22.8 mL | Standard Deviation 21.1 |
| Placebo | 24-hour Sputum Volume | Day 8 | 30.0 mL | Standard Deviation 24.1 |
| Placebo | 24-hour Sputum Volume | Day 84 | 25.9 mL | Standard Deviation 22.9 |
| Placebo | 24-hour Sputum Volume | Day 29 | 27.3 mL | Standard Deviation 32.5 |
Secondary
Change From Baseline in Absolute Neutrophil Count (ANC)
Absolute neutrophil count (ANC) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available.
Time frame: Baseline and up to Day 42
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Absolute Neutrophil Count (ANC) | Day 8 | -0.35 giga/L | Standard Deviation 1.59 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Absolute Neutrophil Count (ANC) | Day 29 | -0.36 giga/L | Standard Deviation 1.69 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Absolute Neutrophil Count (ANC) | Day 42 | -0.28 giga/L | Standard Deviation 1.7 |
| Placebo | Change From Baseline in Absolute Neutrophil Count (ANC) | Day 8 | -0.03 giga/L | Standard Deviation 1.45 |
| Placebo | Change From Baseline in Absolute Neutrophil Count (ANC) | Day 29 | 0.59 giga/L | Standard Deviation 1.97 |
| Placebo | Change From Baseline in Absolute Neutrophil Count (ANC) | Day 42 | 0.24 giga/L | Standard Deviation 2.21 |
Secondary
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Pulmonary function testing (spirometry) was conducted in accordance with American Thoracic Society standards. FEV1 was defined as 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). Imputation method: last observation carried forward (LOCF).
Time frame: Baseline and up to end of study (planned at Day 84)
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 29 | -0.53 Percent of predicted FEV1 | Standard Deviation 7.88 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 56 | 0.81 Percent of predicted FEV1 | Standard Deviation 5.5 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 42 | 1.19 Percent of predicted FEV1 | Standard Deviation 5.88 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 84 | 0.70 Percent of predicted FEV1 | Standard Deviation 5.69 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 8 | -0.67 Percent of predicted FEV1 | Standard Deviation 4.5 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 84 | -0.50 Percent of predicted FEV1 | Standard Deviation 7.62 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 8 | -0.14 Percent of predicted FEV1 | Standard Deviation 5.1 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 29 | -0.22 Percent of predicted FEV1 | Standard Deviation 9.57 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 42 | -0.26 Percent of predicted FEV1 | Standard Deviation 9.88 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 56 | -0.24 Percent of predicted FEV1 | Standard Deviation 9.61 |
Secondary
Change From Baseline in Forced Vital Capacity (FVC)
Pulmonary function testing (spirometry) was conducted in accordance with American Thoracic Society standards. FVC was defined as the maximal volume of air exhaled with maximally forced effort from a maximal inspiration, i.e. vital capacity performed with a maximally forced expiratory effort expressed in liters at BTPS. Imputation method: last observation carried forward (LOCF).
Time frame: Baseline and up to end of study (planned at Day 84)
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) | Day 29 | -0.76 Percent of predicted FVC | Standard Deviation 8.7 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) | Day 56 | 0.36 Percent of predicted FVC | Standard Deviation 7.45 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) | Day 42 | 0.92 Percent of predicted FVC | Standard Deviation 8.98 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) | Day 84 | -0.01 Percent of predicted FVC | Standard Deviation 7.57 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Forced Vital Capacity (FVC) | Day 8 | -0.33 Percent of predicted FVC | Standard Deviation 7.93 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Day 84 | -1.99 Percent of predicted FVC | Standard Deviation 8.86 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Day 8 | 0.04 Percent of predicted FVC | Standard Deviation 7.32 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Day 29 | -1.05 Percent of predicted FVC | Standard Deviation 9.12 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Day 42 | -1.09 Percent of predicted FVC | Standard Deviation 9.46 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Day 56 | -1.16 Percent of predicted FVC | Standard Deviation 9.83 |
Secondary
Change From Baseline in High Sensitive C-reactive Protein (hsCRP)
High sensitive C-reactive protein (hsCRP) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available.
Time frame: Baseline and up to Day 42
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | Day 8 | -0.43 mg/L |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | Day 29 | 0 mg/L |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | Day 42 | -0.16 mg/L |
| Placebo | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | Day 29 | 0 mg/L |
| Placebo | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | Day 42 | 0.12 mg/L |
| Placebo | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | Day 8 | -0.19 mg/L |
Secondary
Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS)
Participants completed the Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS). They were assured that all data would be treated confidentially and that the answers would not have any influence on study drug treatment. Participants completed the questionnaires on their own in a quiet area, without discussing them with study staff or accompanying persons (e.g. friends or relatives) and before being seen by the clinician. The score ranges between 1 and 7, 1 being the worst possible score.
Time frame: Up to end of study (planned at Day 84)
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) | Day 1 | 4.88 Total score on a scale | Standard Deviation 1.2 |
| Ciprofloxacin Inhale (BAYQ3939) | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) | Day 29 | 4.99 Total score on a scale | Standard Deviation 1.21 |
| Ciprofloxacin Inhale (BAYQ3939) | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) | Day 56 | 4.94 Total score on a scale | Standard Deviation 1.29 |
| Ciprofloxacin Inhale (BAYQ3939) | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) | Day 84 | 5.01 Total score on a scale | Standard Deviation 1.21 |
| Placebo | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) | Day 84 | 4.99 Total score on a scale | Standard Deviation 1.06 |
| Placebo | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) | Day 1 | 4.96 Total score on a scale | Standard Deviation 0.98 |
| Placebo | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) | Day 56 | 4.91 Total score on a scale | Standard Deviation 1.16 |
| Placebo | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) | Day 29 | 4.93 Total score on a scale | Standard Deviation 1.21 |
Secondary
Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score
Participants completed the Saint George's Respiratory Questionnaire (SGRQ). They were assured that all data would be treated confidentially and that the answers would not have any influence on study drug treatment. Participants completed the questionnaires on their own in a quiet area, without discussing them with study staff or accompanying persons (e.g. friends or relatives) and before being seen by the clinician. The score ranges from 0 to 100 with 100 being the worst possible score.
Time frame: Up to end of study (planned at Day 84)
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score | Day 1 | 43.8 Scores on a scale | Standard Deviation 20.3 |
| Ciprofloxacin Inhale (BAYQ3939) | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score | Day 29 | 41.5 Scores on a scale | Standard Deviation 21 |
| Ciprofloxacin Inhale (BAYQ3939) | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score | Day 56 | 40.6 Scores on a scale | Standard Deviation 20.9 |
| Ciprofloxacin Inhale (BAYQ3939) | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score | Day 84 | 40.6 Scores on a scale | Standard Deviation 18.1 |
| Placebo | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score | Day 84 | 41.6 Scores on a scale | Standard Deviation 17 |
| Placebo | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score | Day 1 | 44.7 Scores on a scale | Standard Deviation 18.1 |
| Placebo | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score | Day 56 | 44.1 Scores on a scale | Standard Deviation 18.6 |
| Placebo | Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score | Day 29 | 44.8 Scores on a scale | Standard Deviation 19.8 |
Secondary
Emergence of New Potential Respiratory Pathogens
The emergence of new potential respiratory pathogens was evaluated using microbiological analysis. Evaluated was the cumulative number of participants with first appearance of new potential respiratory antigens at each time point. In some cases, participants attended the end of study visit later than Day 84 (up to Day 88).
Time frame: Up to end of study (planned at Day 84)
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 14 | 7 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 5 | 1 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 7 | 2 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 8 | 7 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 9 | 7 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 10 | 7 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 4 | 1 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 15 | 7 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 28 | 7 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 29 | 12 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 30 | 14 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 36 | 15 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 39 | 16 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 42 | 18 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 43 | 21 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 44 | 25 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 45 | 26 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 57 | 29 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 58 | 29 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 59 | 30 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 78 | 31 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 83 | 32 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 84 | 33 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 85 | 38 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 86 | 41 Cumulative participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of New Potential Respiratory Pathogens | Day 88 | 43 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 59 | 47 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 4 | 0 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 42 | 33 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 5 | 2 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 86 | 54 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 7 | 2 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 43 | 38 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 8 | 8 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 78 | 47 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 9 | 10 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 44 | 40 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 10 | 11 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 85 | 53 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 14 | 12 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 45 | 41 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 15 | 13 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 83 | 47 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 28 | 14 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 57 | 45 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 29 | 24 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 88 | 54 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 30 | 30 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 58 | 46 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 36 | 30 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 84 | 47 Cumulative participants |
| Placebo | Emergence of New Potential Respiratory Pathogens | Day 39 | 31 Cumulative participants |
Secondary
Emergence of Resistance Among Baseline Pathogens
The emergence of resistance (at least two-fold increase of Minimal inhibitory concentration, MIC, vs. baseline values) probably or possibly related to study medication among baseline pathogens was evaluated using microbiological analysis.
Time frame: Up to end of study (planned at Day 84)
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of Resistance Among Baseline Pathogens | Emergence (>= 2* increase of MIC) | 7 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of Resistance Among Baseline Pathogens | Sustained (>= 2* increase of MIC until end) | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of Resistance Among Baseline Pathogens | Transient (Increase in MIC with normalization) | 5 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Emergence of Resistance Among Baseline Pathogens | Insufficient follow up | 1 Participants |
| Placebo | Emergence of Resistance Among Baseline Pathogens | Insufficient follow up | 0 Participants |
| Placebo | Emergence of Resistance Among Baseline Pathogens | Emergence (>= 2* increase of MIC) | 1 Participants |
| Placebo | Emergence of Resistance Among Baseline Pathogens | Transient (Increase in MIC with normalization) | 1 Participants |
| Placebo | Emergence of Resistance Among Baseline Pathogens | Sustained (>= 2* increase of MIC until end) | 0 Participants |
Secondary
Microbiological Response of Cipro Inhale Per Participant
Microbiological response was defined as reduction in bacterial load or eradication (measured as the percentage of participants with positive culture). Missing values were not imputed.
Time frame: Up to end of study (planned at Day 84)
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Participant | Day 1 | 100.0 Percentage of participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Participant | Day 8 | 52.4 Percentage of participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Participant | Day 29 | 65.0 Percentage of participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Participant | Day 42 | 83.3 Percentage of participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Participant | Day 56 | 87.1 Percentage of participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Participant | Day 84 | 85.2 Percentage of participants |
| Placebo | Microbiological Response of Cipro Inhale Per Participant | Day 56 | 96.4 Percentage of participants |
| Placebo | Microbiological Response of Cipro Inhale Per Participant | Day 1 | 100.0 Percentage of participants |
| Placebo | Microbiological Response of Cipro Inhale Per Participant | Day 42 | 86.8 Percentage of participants |
| Placebo | Microbiological Response of Cipro Inhale Per Participant | Day 8 | 88.2 Percentage of participants |
| Placebo | Microbiological Response of Cipro Inhale Per Participant | Day 84 | 92.0 Percentage of participants |
| Placebo | Microbiological Response of Cipro Inhale Per Participant | Day 29 | 91.8 Percentage of participants |
Secondary
Microbiological Response of Cipro Inhale Per Pathogen
Microbiological response was defined as reduction in bacterial load or eradication (measured as the number of participants with positive culture). Missing values were not imputed. Pathogens analyzed: Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Serratia marcescens, Pseudomonas aeruginosa, mucoid, Pseudomonas aeruginosa, non mucoid, Stenotrophomonas maltophilia, Achromobacter xylosoxydans, Moraxella catarrhalis, Haemophilus influenzae
Time frame: Up to end of study (planned at Day 84)
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | K. oxytoca Day 1 | 3 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, mucoid Day 29 | 9 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, mucoid Day 42 | 9 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, mucoid Day 56 | 6 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, mucoid Day 84 | 4 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, non mucoid Day 1 | 20 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, non mucoid Day 8 | 6 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, non mucoid Day 29 | 10 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, non mucoid Day 42 | 12 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, non mucoid Day 56 | 10 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, non mucoid Day 84 | 13 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. maltophilia Day 1 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. maltophilia Day 8 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. maltophilia Day 29 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. maltophilia Day 42 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. maltophilia Day 56 | 4 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. maltophilia Day 84 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | A. xylosoxydans Day 1 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | A. xylosoxydans Day 8 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | A. xylosoxydans Day 29 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | A. xylosoxydans Day 42 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | A. xylosoxydans Day 56 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | A. xylosoxydans Day 84 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | M. catarrhalis Day 1 | 5 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | M. catarrhalis Day 8 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | M. catarrhalis Day 29 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | M. catarrhalis Day 42 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | M. catarrhalis Day 56 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | M. catarrhalis Day 84 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | H. influenzae Day 1 | 14 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | H. influenzae Day 8 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | H. influenzae Day 29 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | H. influenzae Day 42 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | H. influenzae Day 56 | 3 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | H. influenzae Day 84 | 4 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. aureus Day 1 | 8 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. aureus Day 8 | 4 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. aureus Day 29 | 5 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. aureus Day 42 | 6 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. aureus Day 56 | 8 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. aureus Day 84 | 5 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. pneumoniae Day 1 | 7 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. pneumoniae Day 8 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. pneumoniae Day 29 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. pneumoniae Day 42 | 3 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. pneumoniae Day 56 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. pneumoniae Day 84 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | E. coli Day 1 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | E. coli Day 8 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | E. coli Day 29 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | E. coli Day 42 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | E. coli Day 56 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | E. coli Day 84 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | K. pneumoniae Day 1 | 5 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | K. pneumoniae Day 8 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | K. pneumoniae Day 29 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | K. pneumoniae Day 42 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | K. pneumoniae Day 56 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | K. pneumoniae Day 84 | 3 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | K. oxytoca Day 8 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | K. oxytoca Day 29 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | K. oxytoca Day 42 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | K. oxytoca Day 56 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | K. oxytoca Day 84 | 1 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. mirabilis Day 1 | 3 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. mirabilis Day 8 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. mirabilis Day 29 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. mirabilis Day 42 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. mirabilis Day 56 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. mirabilis Day 84 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. marcescens Day 1 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. marcescens Day 8 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. marcescens Day 29 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. marcescens Day 42 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. marcescens Day 56 | 0 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | S. marcescens Day 84 | 2 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, mucoid Day 1 | 12 Participants |
| Ciprofloxacin Inhale (BAYQ3939) | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, mucoid Day 8 | 7 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. aureus Day 56 | 5 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | K. oxytoca Day 1 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, mucoid Day 29 | 16 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. aureus Day 84 | 5 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, mucoid Day 42 | 12 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. marcescens Day 29 | 3 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, mucoid Day 56 | 6 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. pneumoniae Day 1 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, mucoid Day 84 | 5 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | K. oxytoca Day 8 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, non mucoid Day 1 | 19 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. pneumoniae Day 8 | 4 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, non mucoid Day 8 | 17 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. mirabilis Day 56 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, non mucoid Day 29 | 14 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. pneumoniae Day 29 | 4 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, non mucoid Day 42 | 12 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | K. oxytoca Day 29 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, non mucoid Day 56 | 9 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. pneumoniae Day 42 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, non mucoid Day 84 | 6 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, mucoid Day 1 | 16 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. maltophilia Day 1 | 3 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. pneumoniae Day 56 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. maltophilia Day 8 | 3 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | K. oxytoca Day 42 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. maltophilia Day 29 | 3 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. pneumoniae Day 84 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. maltophilia Day 42 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. mirabilis Day 84 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. maltophilia Day 56 | 3 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | E. coli Day 1 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. maltophilia Day 84 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | K. oxytoca Day 56 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | A. xylosoxydans Day 1 | 3 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | E. coli Day 8 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | A. xylosoxydans Day 8 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. marcescens Day 42 | 3 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | A. xylosoxydans Day 29 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | E. coli Day 29 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | A. xylosoxydans Day 42 | 0 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | K. oxytoca Day 84 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | A. xylosoxydans Day 56 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | E. coli Day 42 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | A. xylosoxydans Day 84 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. marcescens Day 1 | 3 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | M. catarrhalis Day 1 | 3 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | E. coli Day 56 | 0 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | M. catarrhalis Day 8 | 3 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. mirabilis Day 1 | 4 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | M. catarrhalis Day 29 | 6 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | E. coli Day 84 | 0 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | M. catarrhalis Day 42 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. marcescens Day 84 | 0 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | M. catarrhalis Day 56 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | K. pneumoniae Day 1 | 0 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | M. catarrhalis Day 84 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. mirabilis Day 8 | 3 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | H. influenzae Day 1 | 16 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | K. pneumoniae Day 8 | 0 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | H. influenzae Day 8 | 12 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. marcescens Day 8 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | H. influenzae Day 29 | 11 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | K. pneumoniae Day 29 | 0 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | H. influenzae Day 42 | 7 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. mirabilis Day 29 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | H. influenzae Day 56 | 8 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | K. pneumoniae Day 42 | 1 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | H. influenzae Day 84 | 8 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. marcescens Day 56 | 2 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. aureus Day 1 | 17 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | K. pneumoniae Day 56 | 0 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. aureus Day 8 | 7 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. mirabilis Day 42 | 3 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. aureus Day 29 | 10 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | K. pneumoniae Day 84 | 0 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | S. aureus Day 42 | 9 Participants |
| Placebo | Microbiological Response of Cipro Inhale Per Pathogen | P. aeruginosa, mucoid Day 8 | 15 Participants |
Secondary
Time to Exacerbation With Antibiotic Intervention
Acute exacerbation was defined according to the joint American Thoracic Society/European Respiratory Society criteria. For detailed information with regard to this definition of acute exacerbation, please refer to the detailed description in the protocol section. The time to an acute exacerbation with antibiotic intervention was determined.
Time frame: Up to end of study (planned at Day 84)
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants. NA: due to fewer than 25% of participants having an exacerbation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Time to Exacerbation With Antibiotic Intervention | NA Days |
| Placebo | Time to Exacerbation With Antibiotic Intervention | NA Days |
Other Pre-specified
Change From Baseline in Total Bacterial Load in the Sputum
Total bacterial load was determined in sputum collected before the inhalation of study drug. Sputum samples were either provided by the participant during the respective study visit, or participants had to bring a sputum sample that had been produced within the 4 hours prior to the visit. Induced sputum samples could be collected if the participant was unable to produce a spontaneously expectorated sputum sample of \> 2 mL on Day 8. Imputation method: last observation carried forward (LOCF). CFU: colony forming units, log10: decadic logarithm
Time frame: Baseline and up to end of study (planned at Day 84)
Population: Modified intent-to-treat (ITT) analyses were performed on all participants who had been randomized and received study drug. This population was identical to the ITT population of all randomized participants. Decadic logarithm of colony forming units (CFUs) per gram sputum
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Total Bacterial Load in the Sputum | Day 8 | -2.87 log10 of CFU per gram sputum | Standard Deviation 3.39 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Total Bacterial Load in the Sputum | Day 42 | -1.86 log10 of CFU per gram sputum | Standard Deviation 3.06 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Total Bacterial Load in the Sputum | Day 56 | -1.86 log10 of CFU per gram sputum | Standard Deviation 3.11 |
| Ciprofloxacin Inhale (BAYQ3939) | Change From Baseline in Total Bacterial Load in the Sputum | Day 84 | -1.37 log10 of CFU per gram sputum | Standard Deviation 3.17 |
| Placebo | Change From Baseline in Total Bacterial Load in the Sputum | Day 84 | -0.24 log10 of CFU per gram sputum | Standard Deviation 1.77 |
| Placebo | Change From Baseline in Total Bacterial Load in the Sputum | Day 8 | -0.20 log10 of CFU per gram sputum | Standard Deviation 2.15 |
| Placebo | Change From Baseline in Total Bacterial Load in the Sputum | Day 56 | -0.21 log10 of CFU per gram sputum | Standard Deviation 1.89 |
| Placebo | Change From Baseline in Total Bacterial Load in the Sputum | Day 42 | -0.31 log10 of CFU per gram sputum | Standard Deviation 2.08 |