Trial Outcomes & Findings for Evaluation of Cipro Inhale in Patients With Non-cystic Fibrosis Bronchiectasis (NCT NCT00930982)
NCT ID: NCT00930982
Last Updated: 2014-12-12
Results Overview
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
COMPLETED
PHASE2
124 participants
Baseline and 29 days
2014-12-12
Participant Flow
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.
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).
Participant milestones
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Overall Study
STARTED
|
60
|
64
|
|
Overall Study
COMPLETED
|
39
|
35
|
|
Overall Study
NOT COMPLETED
|
21
|
29
|
Reasons for withdrawal
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Overall Study
Adverse Event
|
19
|
23
|
|
Overall Study
Protocol Violation
|
1
|
5
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
Evaluation of Cipro Inhale in Patients With Non-cystic Fibrosis Bronchiectasis
Baseline characteristics by cohort
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
Total
n=124 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.7 Years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
61.4 Years
STANDARD_DEVIATION 11.9 • n=7 Participants
|
63.0 Years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
82 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 29 daysPopulation: 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.
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
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
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 3.40
|
-0.32 log10 of CFU per gram sputum
Standard Deviation 2.29
|
SECONDARY outcome
Timeframe: 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.
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).
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Day 8
|
-0.67 Percent of predicted FEV1
Standard Deviation 4.50
|
-0.14 Percent of predicted FEV1
Standard Deviation 5.10
|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Day 29
|
-0.53 Percent of predicted FEV1
Standard Deviation 7.88
|
-0.22 Percent of predicted FEV1
Standard Deviation 9.57
|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Day 42
|
1.19 Percent of predicted FEV1
Standard Deviation 5.88
|
-0.26 Percent of predicted FEV1
Standard Deviation 9.88
|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Day 56
|
0.81 Percent of predicted FEV1
Standard Deviation 5.50
|
-0.24 Percent of predicted FEV1
Standard Deviation 9.61
|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Day 84
|
0.70 Percent of predicted FEV1
Standard Deviation 5.69
|
-0.50 Percent of predicted FEV1
Standard Deviation 7.62
|
SECONDARY outcome
Timeframe: 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.
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).
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Change From Baseline in Forced Vital Capacity (FVC)
Day 8
|
-0.33 Percent of predicted FVC
Standard Deviation 7.93
|
0.04 Percent of predicted FVC
Standard Deviation 7.32
|
|
Change From Baseline in Forced Vital Capacity (FVC)
Day 29
|
-0.76 Percent of predicted FVC
Standard Deviation 8.70
|
-1.05 Percent of predicted FVC
Standard Deviation 9.12
|
|
Change From Baseline in Forced Vital Capacity (FVC)
Day 42
|
0.92 Percent of predicted FVC
Standard Deviation 8.98
|
-1.09 Percent of predicted FVC
Standard Deviation 9.46
|
|
Change From Baseline in Forced Vital Capacity (FVC)
Day 56
|
0.36 Percent of predicted FVC
Standard Deviation 7.45
|
-1.16 Percent of predicted FVC
Standard Deviation 9.83
|
|
Change From Baseline in Forced Vital Capacity (FVC)
Day 84
|
-0.01 Percent of predicted FVC
Standard Deviation 7.57
|
-1.99 Percent of predicted FVC
Standard Deviation 8.86
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Time to Exacerbation With Antibiotic Intervention
|
NA Days
NA: due to fewer than 25% of participants having an exacerbation
|
NA Days
NA: due to fewer than 25% of participants having an exacerbation
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
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
|
44.7 Scores on a scale
Standard Deviation 18.1
|
|
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 21.0
|
44.8 Scores on a scale
Standard Deviation 19.8
|
|
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
|
44.1 Scores on a scale
Standard Deviation 18.6
|
|
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
|
41.6 Scores on a scale
Standard Deviation 17.0
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
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 1.20
|
4.96 Total score on a scale
Standard Deviation 0.98
|
|
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
|
4.93 Total score on a scale
Standard Deviation 1.21
|
|
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
|
4.91 Total score on a scale
Standard Deviation 1.16
|
|
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
|
4.99 Total score on a scale
Standard Deviation 1.06
|
SECONDARY outcome
Timeframe: Baseline and up to Day 42Population: 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.
High sensitive C-reactive protein (hsCRP) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available.
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Change From Baseline in High Sensitive C-reactive Protein (hsCRP)
Day 8
|
-0.43 mg/L
Interval -4.1 to 0.4
|
-0.19 mg/L
Interval -2.48 to -0.19
|
|
Change From Baseline in High Sensitive C-reactive Protein (hsCRP)
Day 29
|
0 mg/L
Interval -3.5 to 1.9
|
0 mg/L
Interval -1.92 to 3.1
|
|
Change From Baseline in High Sensitive C-reactive Protein (hsCRP)
Day 42
|
-0.16 mg/L
Interval -4.4 to 1.91
|
0.12 mg/L
Interval -2.07 to 3.1
|
SECONDARY outcome
Timeframe: Baseline and up to Day 42Population: 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.
Absolute neutrophil count (ANC) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available.
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Change From Baseline in Absolute Neutrophil Count (ANC)
Day 8
|
-0.35 giga/L
Standard Deviation 1.59
|
-0.03 giga/L
Standard Deviation 1.45
|
|
Change From Baseline in Absolute Neutrophil Count (ANC)
Day 29
|
-0.36 giga/L
Standard Deviation 1.69
|
0.59 giga/L
Standard Deviation 1.97
|
|
Change From Baseline in Absolute Neutrophil Count (ANC)
Day 42
|
-0.28 giga/L
Standard Deviation 1.70
|
0.24 giga/L
Standard Deviation 2.21
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
24-hour Sputum Volume
Day 1
|
24.9 mL
Standard Deviation 23.6
|
30.2 mL
Standard Deviation 25.2
|
|
24-hour Sputum Volume
Day 8
|
18.9 mL
Standard Deviation 22.2
|
30.0 mL
Standard Deviation 24.1
|
|
24-hour Sputum Volume
Day 29
|
20.5 mL
Standard Deviation 25.3
|
27.3 mL
Standard Deviation 32.5
|
|
24-hour Sputum Volume
Day 42
|
21.1 mL
Standard Deviation 24.7
|
22.8 mL
Standard Deviation 21.1
|
|
24-hour Sputum Volume
Day 56
|
19.6 mL
Standard Deviation 24.8
|
22.0 mL
Standard Deviation 24.8
|
|
24-hour Sputum Volume
Day 84
|
23.6 mL
Standard Deviation 28.9
|
25.9 mL
Standard Deviation 22.9
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
24-hour Sputum Color (Percentage of Participants With Non-clear Sputum)
Day 1
|
91.7 Percentage of participants
|
88.9 Percentage of participants
|
|
24-hour Sputum Color (Percentage of Participants With Non-clear Sputum)
Day 8
|
73.2 Percentage of participants
|
94.9 Percentage of participants
|
|
24-hour Sputum Color (Percentage of Participants With Non-clear Sputum)
Day 29
|
75.5 Percentage of participants
|
82.7 Percentage of participants
|
|
24-hour Sputum Color (Percentage of Participants With Non-clear Sputum)
Day 42
|
72.8 Percentage of participants
|
88.4 Percentage of participants
|
|
24-hour Sputum Color (Percentage of Participants With Non-clear Sputum)
Day 56
|
75.0 Percentage of participants
|
86.5 Percentage of participants
|
|
24-hour Sputum Color (Percentage of Participants With Non-clear Sputum)
Day 84
|
66.6 Percentage of participants
|
72.8 Percentage of participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Microbiological Response of Cipro Inhale Per Participant
Day 1
|
100.0 Percentage of participants
|
100.0 Percentage of participants
|
|
Microbiological Response of Cipro Inhale Per Participant
Day 8
|
52.4 Percentage of participants
|
88.2 Percentage of participants
|
|
Microbiological Response of Cipro Inhale Per Participant
Day 29
|
65.0 Percentage of participants
|
91.8 Percentage of participants
|
|
Microbiological Response of Cipro Inhale Per Participant
Day 42
|
83.3 Percentage of participants
|
86.8 Percentage of participants
|
|
Microbiological Response of Cipro Inhale Per Participant
Day 56
|
87.1 Percentage of participants
|
96.4 Percentage of participants
|
|
Microbiological Response of Cipro Inhale Per Participant
Day 84
|
85.2 Percentage of participants
|
92.0 Percentage of participants
|
SECONDARY outcome
Timeframe: 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.
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
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. aureus Day 1
|
8 Participants
|
17 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. aureus Day 8
|
4 Participants
|
7 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. aureus Day 29
|
5 Participants
|
10 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. aureus Day 42
|
6 Participants
|
9 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. aureus Day 56
|
8 Participants
|
5 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. aureus Day 84
|
5 Participants
|
5 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. pneumoniae Day 1
|
7 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. pneumoniae Day 8
|
2 Participants
|
4 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. pneumoniae Day 29
|
0 Participants
|
4 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. pneumoniae Day 42
|
3 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. pneumoniae Day 56
|
1 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. pneumoniae Day 84
|
1 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
E. coli Day 1
|
2 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
E. coli Day 8
|
2 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
E. coli Day 29
|
2 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
E. coli Day 42
|
0 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
E. coli Day 56
|
1 Participants
|
0 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
E. coli Day 84
|
1 Participants
|
0 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
K. pneumoniae Day 1
|
5 Participants
|
0 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
K. pneumoniae Day 8
|
0 Participants
|
0 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
K. pneumoniae Day 29
|
0 Participants
|
0 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
K. pneumoniae Day 42
|
0 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
K. pneumoniae Day 56
|
1 Participants
|
0 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
K. pneumoniae Day 84
|
3 Participants
|
0 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
K. oxytoca Day 1
|
3 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
K. oxytoca Day 8
|
0 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
K. oxytoca Day 29
|
0 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
K. oxytoca Day 42
|
0 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
K. oxytoca Day 56
|
0 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
K. oxytoca Day 84
|
1 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. mirabilis Day 1
|
3 Participants
|
4 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. mirabilis Day 8
|
0 Participants
|
3 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. mirabilis Day 29
|
0 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. mirabilis Day 42
|
2 Participants
|
3 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. mirabilis Day 56
|
2 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. mirabilis Day 84
|
2 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. marcescens Day 1
|
2 Participants
|
3 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. marcescens Day 8
|
0 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. marcescens Day 29
|
0 Participants
|
3 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. marcescens Day 42
|
0 Participants
|
3 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. marcescens Day 56
|
0 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. marcescens Day 84
|
2 Participants
|
0 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. aeruginosa, mucoid Day 1
|
12 Participants
|
16 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. aeruginosa, mucoid Day 8
|
7 Participants
|
15 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. aeruginosa, mucoid Day 29
|
9 Participants
|
16 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. aeruginosa, mucoid Day 42
|
9 Participants
|
12 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. aeruginosa, mucoid Day 56
|
6 Participants
|
6 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. aeruginosa, mucoid Day 84
|
4 Participants
|
5 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. aeruginosa, non mucoid Day 1
|
20 Participants
|
19 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. aeruginosa, non mucoid Day 8
|
6 Participants
|
17 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. aeruginosa, non mucoid Day 29
|
10 Participants
|
14 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. aeruginosa, non mucoid Day 42
|
12 Participants
|
12 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. aeruginosa, non mucoid Day 56
|
10 Participants
|
9 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
P. aeruginosa, non mucoid Day 84
|
13 Participants
|
6 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. maltophilia Day 1
|
2 Participants
|
3 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. maltophilia Day 8
|
0 Participants
|
3 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. maltophilia Day 29
|
2 Participants
|
3 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. maltophilia Day 42
|
2 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. maltophilia Day 56
|
4 Participants
|
3 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
S. maltophilia Day 84
|
1 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
A. xylosoxydans Day 1
|
2 Participants
|
3 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
A. xylosoxydans Day 8
|
2 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
A. xylosoxydans Day 29
|
2 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
A. xylosoxydans Day 42
|
2 Participants
|
0 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
A. xylosoxydans Day 56
|
1 Participants
|
1 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
A. xylosoxydans Day 84
|
0 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
M. catarrhalis Day 1
|
5 Participants
|
3 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
M. catarrhalis Day 8
|
0 Participants
|
3 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
M. catarrhalis Day 29
|
0 Participants
|
6 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
M. catarrhalis Day 42
|
1 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
M. catarrhalis Day 56
|
1 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
M. catarrhalis Day 84
|
1 Participants
|
2 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
H. influenzae Day 1
|
14 Participants
|
16 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
H. influenzae Day 8
|
1 Participants
|
12 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
H. influenzae Day 29
|
1 Participants
|
11 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
H. influenzae Day 42
|
1 Participants
|
7 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
H. influenzae Day 56
|
3 Participants
|
8 Participants
|
|
Microbiological Response of Cipro Inhale Per Pathogen
H. influenzae Day 84
|
4 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: 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.
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).
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Emergence of New Potential Respiratory Pathogens
Day 4
|
1 Cumulative participants
|
0 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 5
|
1 Cumulative participants
|
2 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 7
|
2 Cumulative participants
|
2 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 8
|
7 Cumulative participants
|
8 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 9
|
7 Cumulative participants
|
10 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 10
|
7 Cumulative participants
|
11 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 14
|
7 Cumulative participants
|
12 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 15
|
7 Cumulative participants
|
13 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 28
|
7 Cumulative participants
|
14 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 29
|
12 Cumulative participants
|
24 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 30
|
14 Cumulative participants
|
30 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 36
|
15 Cumulative participants
|
30 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 39
|
16 Cumulative participants
|
31 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 42
|
18 Cumulative participants
|
33 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 43
|
21 Cumulative participants
|
38 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 44
|
25 Cumulative participants
|
40 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 45
|
26 Cumulative participants
|
41 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 57
|
29 Cumulative participants
|
45 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 58
|
29 Cumulative participants
|
46 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 59
|
30 Cumulative participants
|
47 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 78
|
31 Cumulative participants
|
47 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 83
|
32 Cumulative participants
|
47 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 84
|
33 Cumulative participants
|
47 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 85
|
38 Cumulative participants
|
53 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 86
|
41 Cumulative participants
|
54 Cumulative participants
|
|
Emergence of New Potential Respiratory Pathogens
Day 88
|
43 Cumulative participants
|
54 Cumulative participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Emergence of Resistance Among Baseline Pathogens
Emergence (>= 2* increase of MIC)
|
7 Participants
|
1 Participants
|
|
Emergence of Resistance Among Baseline Pathogens
Sustained (>= 2* increase of MIC until end)
|
1 Participants
|
0 Participants
|
|
Emergence of Resistance Among Baseline Pathogens
Transient (Increase in MIC with normalization)
|
5 Participants
|
1 Participants
|
|
Emergence of Resistance Among Baseline Pathogens
Insufficient follow up
|
1 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 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
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
Outcome measures
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 Participants
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 Participants
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Change From Baseline in Total Bacterial Load in the Sputum
Day 8
|
-2.87 log10 of CFU per gram sputum
Standard Deviation 3.39
|
-0.20 log10 of CFU per gram sputum
Standard Deviation 2.15
|
|
Change From Baseline in Total Bacterial Load in the Sputum
Day 42
|
-1.86 log10 of CFU per gram sputum
Standard Deviation 3.06
|
-0.31 log10 of CFU per gram sputum
Standard Deviation 2.08
|
|
Change From Baseline in Total Bacterial Load in the Sputum
Day 56
|
-1.86 log10 of CFU per gram sputum
Standard Deviation 3.11
|
-0.21 log10 of CFU per gram sputum
Standard Deviation 1.89
|
|
Change From Baseline in Total Bacterial Load in the Sputum
Day 84
|
-1.37 log10 of CFU per gram sputum
Standard Deviation 3.17
|
-0.24 log10 of CFU per gram sputum
Standard Deviation 1.77
|
Adverse Events
Ciprofloxacin Inhale (BAYQ3939)
Placebo
Serious adverse events
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 participants at risk
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 participants at risk
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/60
|
1.6%
1/64 • Number of events 1
|
|
Infections and infestations
Bronchiectasis
|
1.7%
1/60 • Number of events 1
|
7.8%
5/64 • Number of events 6
|
|
Infections and infestations
Sepsis
|
0.00%
0/60
|
1.6%
1/64 • Number of events 1
|
|
Investigations
Catheterisation cardiac
|
0.00%
0/60
|
1.6%
1/64 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal adenocarcinoma
|
1.7%
1/60 • Number of events 1
|
0.00%
0/64
|
|
Nervous system disorders
Complex regional pain syndrome
|
1.7%
1/60 • Number of events 1
|
0.00%
0/64
|
|
Psychiatric disorders
Hallucination
|
1.7%
1/60 • Number of events 1
|
0.00%
0/64
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/60
|
1.6%
1/64 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/60
|
1.6%
1/64 • Number of events 1
|
Other adverse events
| Measure |
Ciprofloxacin Inhale (BAYQ3939)
n=60 participants at risk
32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily
|
Placebo
n=64 participants at risk
Inhalation of matching placebo twice a day
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
5.0%
3/60 • Number of events 3
|
3.1%
2/64 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
5.0%
3/60 • Number of events 3
|
0.00%
0/64
|
|
General disorders
Product taste abnormal
|
13.3%
8/60 • Number of events 8
|
10.9%
7/64 • Number of events 7
|
|
Infections and infestations
Bronchiectasis
|
36.7%
22/60 • Number of events 24
|
34.4%
22/64 • Number of events 23
|
|
Nervous system disorders
Dysgeusia
|
6.7%
4/60 • Number of events 4
|
1.6%
1/64 • Number of events 1
|
|
Nervous system disorders
Headache
|
10.0%
6/60 • Number of events 7
|
9.4%
6/64 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
5.0%
3/60 • Number of events 3
|
4.7%
3/64 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.3%
2/60 • Number of events 2
|
7.8%
5/64 • Number of events 5
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator must send a draft manuscript of the publication or abstract to the sponsor 30 days in advance of submission in order to obtain written approval prior to submission of the final version for publication. This will be reviewed promptly and approval will not be withheld unreasonably. In case of a difference of opinion, the contents of the publication will be discussed in order to find a solution that satisfies both parties.
- Publication restrictions are in place
Restriction type: OTHER