Trial Outcomes & Findings for Study to Evaluate the Safety and Efficacy of Ciprofloxacin (Inhaled) in Patients With Cystic Fibrosis (NCT NCT00645788)
NCT ID: NCT00645788
Last Updated: 2014-06-09
Results Overview
FEV1: The maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters at body temperature and ambient pressure saturated with water vapor (BTPS). This was recorded at the site using a spirometer. The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
288 participants
Primary outcome timeframe
Baseline and End of treatment (Day 28-30)
Results posted on
2014-06-09
Participant Flow
The first visit of the first subject was on 05 May 2008 and the last visit of the last subject on 25 Jan 2011. This study was conducted at 73 centers from 8 countries.
Of all enrolled 486 subjects, 188 had screening failures, the remaining 288 were randomized but 2 subjects (one each in 32.5 mg Ciprofloxacin DPI (Dry Powder for Inhalation) and 48.75 mg Ciprofloxacin DPI groups) did not receive any study drug. A total of 286 subjects received one of the 4 study drug treatments.
Participant milestones
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
32.50 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
94
|
94
|
65
|
35
|
|
Overall Study
Participants Receive Treatment
|
93
|
93
|
65
|
35
|
|
Overall Study
COMPLETED
|
74
|
67
|
47
|
21
|
|
Overall Study
NOT COMPLETED
|
20
|
27
|
18
|
14
|
Reasons for withdrawal
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
32.50 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Overall Study
Did not receive study drug
|
1
|
1
|
0
|
0
|
|
Overall Study
Adverse Event
|
4
|
9
|
5
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
2
|
|
Overall Study
Pulmonary exacerbation
|
13
|
16
|
11
|
9
|
Baseline Characteristics
Study to Evaluate the Safety and Efficacy of Ciprofloxacin (Inhaled) in Patients With Cystic Fibrosis
Baseline characteristics by cohort
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
32.50 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 Participants
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 Participants
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
Total
n=286 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
27.7 Years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
29.3 Years
STANDARD_DEVIATION 9.5 • n=7 Participants
|
31.7 Years
STANDARD_DEVIATION 12.1 • n=5 Participants
|
29.1 Years
STANDARD_DEVIATION 9.4 • n=4 Participants
|
29.3 Years
STANDARD_DEVIATION 10.1 • n=21 Participants
|
|
Sex: Female, Male
Female
|
49 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
133 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
44 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
153 Participants
n=21 Participants
|
|
Forced expiratory volume in 1 second (FEV1)
|
55.0 Percentage of predicted FEV1
STANDARD_DEVIATION 11.3 • n=5 Participants
|
54.7 Percentage of predicted FEV1
STANDARD_DEVIATION 12.3 • n=7 Participants
|
54.8 Percentage of predicted FEV1
STANDARD_DEVIATION 10.6 • n=5 Participants
|
52.7 Percentage of predicted FEV1
STANDARD_DEVIATION 10.7 • n=4 Participants
|
54.6 Percentage of predicted FEV1
STANDARD_DEVIATION 11.4 • n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline and End of treatment (Day 28-30)Population: Intent to treat
FEV1: The maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters at body temperature and ambient pressure saturated with water vapor (BTPS). This was recorded at the site using a spirometer. The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
Outcome measures
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
32.5 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 Participants
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 Participants
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28-30
|
-1.0 Percent of predicted FEV1
Standard Deviation 6.01
|
-0.62 Percent of predicted FEV1
Standard Deviation 5.52
|
-2.2 Percent of predicted FEV1
Standard Deviation 5.47
|
-2.2 Percent of predicted FEV1
Standard Deviation 5.17
|
SECONDARY outcome
Timeframe: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60).Population: Intent to treat
FEV1: The maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters at body temperature and ambient pressure saturated with water vapor (BTPS). This was recorded at the site using a spirometer. The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
Outcome measures
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
32.5 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 Participants
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 Participants
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9
Visit 9
|
-2.0 Percent of predicted FEV1
Standard Deviation 5.22
|
-0.95 Percent of predicted FEV1
Standard Deviation 5.29
|
-1.9 Percent of predicted FEV1
Standard Deviation 4.89
|
-1.6 Percent of predicted FEV1
Standard Deviation 5.13
|
|
Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9
Visit 4
|
0.40 Percent of predicted FEV1
Standard Deviation 5.14
|
0.65 Percent of predicted FEV1
Standard Deviation 4.62
|
-0.84 Percent of predicted FEV1
Standard Deviation 3.92
|
-0.36 Percent of predicted FEV1
Standard Deviation 3.5
|
|
Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9
Visit 5
|
0.10 Percent of predicted FEV1
Standard Deviation 6.14
|
0.26 Percent of predicted FEV1
Standard Deviation 3.94
|
-1.6 Percent of predicted FEV1
Standard Deviation 3.59
|
-0.87 Percent of predicted FEV1
Standard Deviation 4.00
|
|
Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9
Visit 8
|
-1.5 Percent of predicted FEV1
Standard Deviation 5.95
|
-0.71 Percent of predicted FEV1
Standard Deviation 5.14
|
-1.2 Percent of predicted FEV1
Standard Deviation 6.04
|
-1.6 Percent of predicted FEV1
Standard Deviation 5.23
|
SECONDARY outcome
Timeframe: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 7 (Day 28-30), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60).Population: Intent to treat
Density of P. aeruginosa in the sputum is expressed as log10 of colony forming units (CFU)/gram (g). The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
Outcome measures
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
32.5 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 Participants
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 Participants
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9
Visit 4
|
-0.76 log10(cfu/g)
Standard Deviation 2.21
|
-1.1 log10(cfu/g)
Standard Deviation 1.63
|
-0.35 log10(cfu/g)
Standard Deviation 2.09
|
-0.56 log10(cfu/g)
Standard Deviation 2.73
|
|
Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9
Visit 5
|
-0.98 log10(cfu/g)
Standard Deviation 2.51
|
-1.0 log10(cfu/g)
Standard Deviation 2.13
|
0.15 log10(cfu/g)
Standard Deviation 2.06
|
-0.65 log10(cfu/g)
Standard Deviation 2.45
|
|
Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9
Visit 7
|
-0.73 log10(cfu/g)
Standard Deviation 2.57
|
-0.78 log10(cfu/g)
Standard Deviation 2.54
|
-0.07 log10(cfu/g)
Standard Deviation 2.59
|
-0.63 log10(cfu/g)
Standard Deviation 2.15
|
|
Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9
Visit 8
|
-0.26 log10(cfu/g)
Standard Deviation 2.52
|
-0.11 log10(cfu/g)
Standard Deviation 2.39
|
-0.14 log10(cfu/g)
Standard Deviation 2.21
|
-0.00 log10(cfu/g)
Standard Deviation 2.43
|
|
Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9
Visit 9
|
0.13 log10(cfu/g)
Standard Deviation 2.19
|
-0.16 log10(cfu/g)
Standard Deviation 2.26
|
-0.19 log10(cfu/g)
Standard Deviation 2.15
|
0.54 log10(cfu/g)
Standard Deviation 1.69
|
SECONDARY outcome
Timeframe: Up to visit 9 (Day 56-60)Population: Intent to treat
Pulmonary exacerbations: Assessment of pulmonary exacerbation was conducted by the treating physician as part of the physical examination. Pulmonary exacerbation was defined by chest examination findings and any or all of the following symptoms: decreased exercise tolerance, increased cough, increased sputum/cough congestion, school or work absenteeism, increased adventitial sounds on the lung examination, and decreased appetite.
Outcome measures
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
32.5 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 Participants
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 Participants
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Time to First Pulmonary Exacerbation Requiring Intervention
|
NA Days
only 16.1 percent of patients had an exacerbation
|
NA Days
only 17.2 percent of patients had an exacerbation
|
NA Days
only 20.0 percent of patients had an exacerbation
|
NA Days
Interval 43.0 to
only 28.6 percent of patients had an exacerbation
|
SECONDARY outcome
Timeframe: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 7 (Day 28-30), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60).Population: Intent to treat
FVC: The maximal volume of air exhaled with maximally forced effort from a maximal inspiration, ie, vital capacity performed with a maximally forced expiratory effort expressed in liters at BTPS (body temperature and ambient pressure saturated with water vapor). The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
Outcome measures
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
32.5 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 Participants
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 Participants
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9
Visit 4
|
-2.5 Percent of predicted FVC
Standard Deviation 8.97
|
0.22 Percent of predicted FVC
Standard Deviation 5.07
|
-0.94 Percent of predicted FVC
Standard Deviation 5.23
|
-0.45 Percent of predicted FVC
Standard Deviation 4.98
|
|
Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9
Visit 5
|
-2.2 Percent of predicted FVC
Standard Deviation 9.78
|
-0.48 Percent of predicted FVC
Standard Deviation 5.11
|
-1.8 Percent of predicted FVC
Standard Deviation 4.51
|
-1.1 Percent of predicted FVC
Standard Deviation 5.57
|
|
Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9
Visit 7
|
-2.8 Percent of predicted FVC
Standard Deviation 8.91
|
-1.4 Percent of predicted FVC
Standard Deviation 6.04
|
-2.7 Percent of predicted FVC
Standard Deviation 6.97
|
-1.4 Percent of predicted FVC
Standard Deviation 8.41
|
|
Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9
Visit 8
|
-2.6 Percent of predicted FVC
Standard Deviation 8.62
|
-0.65 Percent of predicted FVC
Standard Deviation 6.44
|
-1.6 Percent of predicted FVC
Standard Deviation 7.31
|
0.13 Percent of predicted FVC
Standard Deviation 7.72
|
|
Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9
Visit 9
|
-2.9 Percent of predicted FVC
Standard Deviation 8.54
|
-0.70 Percent of predicted FVC
Standard Deviation 6.64
|
-2.3 Percent of predicted FVC
Standard Deviation 5.63
|
-0.53 Percent of predicted FVC
Standard Deviation 7.37
|
SECONDARY outcome
Timeframe: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 7 (Day 28-30), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60).Population: Intent to treat
FEF 25-75% (also known as the maximum midexpiratory flow \[MMEF\]): The mean forced expiration flow over the middle half of the forced vital capacity (FVC). It was taken from the blow with the largest sum of FEV1 and FVC. The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
Outcome measures
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
32.5 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 Participants
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 Participants
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9
Visit 4
|
2.13 Percent of predicted FEF 25-75%
Standard Deviation 7.12
|
1.09 Percent of predicted FEF 25-75%
Standard Deviation 6.90
|
-1.0 Percent of predicted FEF 25-75%
Standard Deviation 4.65
|
-0.49 Percent of predicted FEF 25-75%
Standard Deviation 4.55
|
|
Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9
Visit 5
|
1.48 Percent of predicted FEF 25-75%
Standard Deviation 8.16
|
0.95 Percent of predicted FEF 25-75%
Standard Deviation 4.73
|
-1.1 Percent of predicted FEF 25-75%
Standard Deviation 4.49
|
-0.89 Percent of predicted FEF 25-75%
Standard Deviation 4.16
|
|
Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9
Visit 7
|
0.24 Percent of predicted FEF 25-75%
Standard Deviation 6.84
|
0.35 Percent of predicted FEF 25-75%
Standard Deviation 5.39
|
-2.1 Percent of predicted FEF 25-75%
Standard Deviation 5.62
|
-1.8 Percent of predicted FEF 25-75%
Standard Deviation 4.73
|
|
Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9
Visit 8
|
0.16 Percent of predicted FEF 25-75%
Standard Deviation 7.56
|
-0.33 Percent of predicted FEF 25-75%
Standard Deviation 5.19
|
-1.2 Percent of predicted FEF 25-75%
Standard Deviation 6.23
|
-1.9 Percent of predicted FEF 25-75%
Standard Deviation 5.31
|
|
Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9
Visit 9
|
-0.46 Percent of predicted FEF 25-75%
Standard Deviation 7.35
|
-0.49 Percent of predicted FEF 25-75%
Standard Deviation 5.55
|
-1.3 Percent of predicted FEF 25-75%
Standard Deviation 5.63
|
-1.4 Percent of predicted FEF 25-75%
Standard Deviation 4.99
|
SECONDARY outcome
Timeframe: Baseline and up to visit 9 (day 56-60)Population: Intent to treat
Susceptibility and resistance assessment of a bacterial isolate was performed using the established Food and Drug Administration (FDA) susceptibility criteria for ciprofloxacin. The susceptibility criteria in mg/L are ≤1 for organisms Enterobacteriaciae, P. aeruginosa, Staphylococcus species and S. pneumoniae. The "susceptible" bacterial species likely responds to typical doses of ciprofloxacin. The resistance criteria for ciprofloxacin in mg/L are ≥4 mg/L for the same organisms. Resistance indicates that the bacteria is less likely to respond to typical doses of ciprofloxacin therapy.
Outcome measures
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
32.5 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 Participants
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 Participants
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates
P.aeruginosa sensitive - baseline
|
70 Participants
|
60 Participants
|
51 Participants
|
30 Participants
|
|
Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates
P.aeruginosa resistant - up to visit 9
|
15 Participants
|
15 Participants
|
11 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Baseline and up to visit 9 (day 56-60)Population: Intent to treat
Susceptibility and resistance assessment of a bacterial isolate was performed using the established Food and Drug Administration (FDA) susceptibility criteria for ciprofloxacin. The susceptibility criteria in mg/L are ≤1 for organisms Enterobacteriaciae, P. aeruginosa, Staphylococcus species and S. pneumoniae. The "susceptible" bacterial species likely responds to typical doses of ciprofloxacin. The resistance criteria for ciprofloxacin in mg/L are ≥4 mg/L for the same organisms. Resistance indicates that the bacteria is less likely to respond to typical doses of ciprofloxacin therapy.
Outcome measures
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
32.5 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 Participants
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 Participants
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates
P.aeruginosa sensitive - baseline
|
72 Participants
|
63 Participants
|
48 Participants
|
23 Participants
|
|
Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates
P.aeruginosa resistant- up to visit 9
|
29 Participants
|
31 Participants
|
19 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Baseline and Visit 7 (Day 28-30) and Visit 9 (Day 56 -60)Population: Intent to treat
The CF quality of life questionnaire revised (CFQ-R), a validated disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents and adults with cystic fibrosis (CF). It is self-administered and consists of 44 items, divided into 12 generic and disease-specific scales. The scale includes physical functioning, role, vitality, emotional functioning, social functioning, body image, eating disturbances, treatment burden, health perceptions, weight, respiratory symptoms, and digestive symptoms. Scale range: 0 to 100 (maximum). Better outcome with higher values.
Outcome measures
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
32.5 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 Participants
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 Participants
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale
Baseline
|
68.0 scores on a scale
Standard Deviation 18.7
|
59.5 scores on a scale
Standard Deviation 19.0
|
61.3 scores on a scale
Standard Deviation 18.6
|
68.3 scores on a scale
Standard Deviation 13.8
|
|
Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale
Visit 7
|
70.8 scores on a scale
Standard Deviation 15.9
|
60.0 scores on a scale
Standard Deviation 19.7
|
58.9 scores on a scale
Standard Deviation 18.7
|
61.6 scores on a scale
Standard Deviation 18.4
|
|
Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale
Visit 9
|
67.2 scores on a scale
Standard Deviation 18.9
|
60.6 scores on a scale
Standard Deviation 20.5
|
61.1 scores on a scale
Standard Deviation 19.8
|
71.2 scores on a scale
Standard Deviation 16.6
|
SECONDARY outcome
Timeframe: Up to visit 7 (Day 28-30)Population: Analysis was not performed due to insufficient data.
Plasma concentrations measured using validated high pressure liquid chromatography-mass specroscopy/mass spectroscopy (HPLC-MS/MS) methods in selected patients at predefined time windows to contribute pharmacokinetic (PK) information for an inter-study population PK evaluation. Sampling window for Plasma: Predose (trough level), \<15 min, 2.0 - 2.5 hour, and 4.0 - 7.0 hours after the end of inhalation. Number of samples vary at different time points.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to visit 7 (Day 28-30)Population: Analysis was not performed due to insufficient data.
Sputum concentrations measured using validated HPLC-MS/MS methods in selected patients to contribute kinetic information for an inter-study population sputum kinetic evaluation. Number of samples vary at different time points.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to visit 9 (Day 56-60)Population: Intent to treat
Bronchospasm reported as adverse event: Bronchospasm defined as \>=15% drop in FEV1, and may also include allergic and excercise-induced bronchospasm. Drug-induced bronchospasm: Treatment-emergent bronchospasm was defined as \>=15% drop in FEV1 in the ITT/safety population. Note: One of the bronchospasm events was considered a serious adverse event, and it was not included under "other" adverse events. A sum of bronchospasm events was 1+6=7.
Outcome measures
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
32.5 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 Participants
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 Participants
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 Participants
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Number of Participants With the Occurrence of Drug Induced Bronchospasms
Reported as Adverse event
|
4 participants
|
7 participants
|
3 participants
|
0 participants
|
|
Number of Participants With the Occurrence of Drug Induced Bronchospasms
Defined as >=15 percent drop in FEV1
|
3 participants
|
3 participants
|
3 participants
|
0 participants
|
Adverse Events
32.50 mg Ciprofloxacin DPI (BAYQ3939)
Serious events: 7 serious events
Other events: 67 other events
Deaths: 0 deaths
48.75 mg Ciprofloxacin DPI (BAYQ3939)
Serious events: 17 serious events
Other events: 74 other events
Deaths: 0 deaths
Matching Placebo for 32.50 mg
Serious events: 7 serious events
Other events: 45 other events
Deaths: 0 deaths
Matching Placebo for 48.75 mg
Serious events: 3 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 participants at risk
32.5 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 participants at risk
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 participants at risk
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 participants at risk
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/93
|
1.1%
1/93
|
0.00%
0/65
|
0.00%
0/35
|
|
Gastrointestinal disorders
Distal intestinal obstruction syndrome
|
0.00%
0/93
|
1.1%
1/93
|
0.00%
0/65
|
0.00%
0/35
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/93
|
2.2%
2/93
|
0.00%
0/65
|
0.00%
0/35
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/93
|
0.00%
0/93
|
1.5%
1/65
|
0.00%
0/35
|
|
Infections and infestations
H1N1 influenza
|
1.1%
1/93
|
0.00%
0/93
|
0.00%
0/65
|
0.00%
0/35
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
5.4%
5/93
|
11.8%
11/93
|
6.2%
4/65
|
8.6%
3/35
|
|
Infections and infestations
Sinusitis
|
0.00%
0/93
|
0.00%
0/93
|
1.5%
1/65
|
0.00%
0/35
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/93
|
1.1%
1/93
|
0.00%
0/65
|
0.00%
0/35
|
|
Nervous system disorders
Syncope
|
1.1%
1/93
|
0.00%
0/93
|
0.00%
0/65
|
0.00%
0/35
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/93
|
1.1%
1/93
|
0.00%
0/65
|
0.00%
0/35
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/93
|
2.2%
2/93
|
1.5%
1/65
|
0.00%
0/35
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/93
|
1.1%
1/93
|
0.00%
0/65
|
0.00%
0/35
|
Other adverse events
| Measure |
32.50 mg Ciprofloxacin DPI (BAYQ3939)
n=93 participants at risk
32.5 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
48.75 mg Ciprofloxacin DPI (BAYQ3939)
n=93 participants at risk
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Matching Placebo for 32.50 mg
n=65 participants at risk
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Matching Placebo for 48.75 mg
n=35 participants at risk
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
2.2%
2/93
|
4.3%
4/93
|
1.5%
1/65
|
5.7%
2/35
|
|
General disorders
Chest discomfort
|
5.4%
5/93
|
4.3%
4/93
|
7.7%
5/65
|
0.00%
0/35
|
|
General disorders
Exercise tolerance decreased
|
2.2%
2/93
|
4.3%
4/93
|
1.5%
1/65
|
5.7%
2/35
|
|
General disorders
Product taste abnormal
|
7.5%
7/93
|
17.2%
16/93
|
6.2%
4/65
|
5.7%
2/35
|
|
General disorders
Pyrexia
|
2.2%
2/93
|
2.2%
2/93
|
6.2%
4/65
|
0.00%
0/35
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
23.7%
22/93
|
19.4%
18/93
|
15.4%
10/65
|
31.4%
11/35
|
|
Infections and infestations
Nasopharyngitis
|
1.1%
1/93
|
6.5%
6/93
|
0.00%
0/65
|
5.7%
2/35
|
|
Infections and infestations
Upper respiratory tract infection
|
4.3%
4/93
|
8.6%
8/93
|
0.00%
0/65
|
2.9%
1/35
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.4%
5/93
|
5.4%
5/93
|
4.6%
3/65
|
2.9%
1/35
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.5%
6/93
|
2.2%
2/93
|
0.00%
0/65
|
2.9%
1/35
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.1%
1/93
|
5.4%
5/93
|
0.00%
0/65
|
0.00%
0/35
|
|
Nervous system disorders
Dysgeusia
|
14.0%
13/93
|
9.7%
9/93
|
6.2%
4/65
|
2.9%
1/35
|
|
Nervous system disorders
Headache
|
1.1%
1/93
|
4.3%
4/93
|
10.8%
7/65
|
5.7%
2/35
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
4.3%
4/93
|
6.5%
6/93
|
4.6%
3/65
|
0.00%
0/35
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.8%
24/93
|
21.5%
20/93
|
33.8%
22/65
|
28.6%
10/35
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.5%
7/93
|
3.2%
3/93
|
3.1%
2/65
|
2.9%
1/35
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
7.5%
7/93
|
7.5%
7/93
|
7.7%
5/65
|
5.7%
2/35
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.4%
5/93
|
2.2%
2/93
|
6.2%
4/65
|
2.9%
1/35
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
4.3%
4/93
|
7.5%
7/93
|
1.5%
1/65
|
0.00%
0/35
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
8.6%
8/93
|
8.6%
8/93
|
3.1%
2/65
|
5.7%
2/35
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
5.4%
5/93
|
3.2%
3/93
|
4.6%
3/65
|
2.9%
1/35
|
|
Respiratory, thoracic and mediastinal disorders
Rhonchi
|
5.4%
5/93
|
3.2%
3/93
|
0.00%
0/65
|
5.7%
2/35
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
12.9%
12/93
|
11.8%
11/93
|
16.9%
11/65
|
14.3%
5/35
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
5.4%
5/93
|
7.5%
7/93
|
3.1%
2/65
|
2.9%
1/35
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The agreed point of publication is 12-18 months after database lock at the earliest. Bayer will have 30-45 days to review publications, and may request an additional publication delay of up to 60 days to allow for filing a Patent Application (if applicable). No publication of single center data should be done prior of publication if multi-center data.
- Publication restrictions are in place
Restriction type: OTHER