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Ciprofloxacin Dry Powder for Inhalation in Non-cystic Fibrosis Bronchiectasis (Non-CF BE) (RESPIRE 1)

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ClinicalTrials.gov Identifier: NCT01764841
Recruitment Status : Completed
First Posted : January 10, 2013
Results First Posted : May 24, 2017
Last Update Posted : January 24, 2018
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Bronchiectasis
Interventions Drug: Ciprofloxacin DPI (BAYQ3939)
Drug: Placebo
Enrollment 416
Recruitment Details Study was conducted at 124 study centers in 14 countries (Argentina, Australia, Denmark, France, Germany, Israel, Italy, Japan, Latvia, New Zealand, Slovakia, Spain, UK and US) between 02 May 2013 (first subject first visit) and 09 March 2016 (last subject last visit).
Pre-assignment Details Overall 902 participants were screened, of them 486 were screen failures, and 416 were randomized, out of which 414 participants were assigned to the treatment. One participant from Ciprofloxacin 14 Days on/off group and one participant from Placebo 28 Days on/off group did not receive the study treatment after initial screening.
Arm/Group Title Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Placebo 28 Days on/Off (Placebo 28) Placebo 14 Days on/Off (Placebo 14)
Hide Arm/Group Description Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles). Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles). Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 cycles). Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 cycles).
Period Title: Overall Study
Started 141 137 70 68
Participants Received Treatment 141 [1] 136 [1] 69 [1] 68 [1]
Completed 118 111 56 49
Not Completed 23 26 14 19
Reason Not Completed
Logistical Difficulties             0             1             0             0
Death             3             0             1             4
No Follow Up             1             0             1             0
Protocol Violation             0             1             0             0
Withdrawal by Subject             16             24             11             15
Lost to Follow-up             3             0             1             0
[1]
safety population
Arm/Group Title Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Placebo 28 Days on/Off (Placebo 28) Placebo 14 Days on/Off (Placebo 14) Total
Hide Arm/Group Description Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles). Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles). Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 cycles). Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 cycles). Total of all reporting groups
Overall Number of Baseline Participants 141 137 70 68 416
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 141 participants 137 participants 70 participants 68 participants 416 participants
64.2  (12.1) 65.2  (13.5) 64  (13.5) 65.5  (12.9) 64.7  (12.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 141 participants 137 participants 70 participants 68 participants 416 participants
Female
101
  71.6%
88
  64.2%
52
  74.3%
44
  64.7%
285
  68.5%
Male
40
  28.4%
49
  35.8%
18
  25.7%
24
  35.3%
131
  31.5%
Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 135 participants 129 participants 67 participants 66 participants 397 participants
60.72  (19.47) 52.51  (21.48) 55.52  (22.07) 58.72  (20.4) 56.84  (20.95)
[1]
Measure Description: The SGRQ was a validated, disease-specific instrument that measures health-related quality of life (HRQoL) in adults with chronic obstructive pulmonary disease (COPD) and asthma and was later validated for use in bronchiectasis. The SGRQ covers 3 dimensions: symptoms, activity and impact on daily life. To determine the outcome, a score ranging from 1 to 100 was calculated for each individual domain and for the total score, and smaller scores indicate better health status. For this baseline measure, the symptoms component score was reported.
[2]
Measure Analysis Population Description: Participants with data available for this measure at baseline.
Quality of Life Questionnaire for Bronchiectasis (QoL-B) Respiratory Symptoms Domain Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 128 participants 120 participants 63 participants 65 participants 376 participants
53.01  (18.71) 57.69  (18.72) 55.82  (18.04) 50.67  (19.59) 54.57  (18.87)
[1]
Measure Description: The QoL-B was a disease-specific questionnaire developed for non-Cystic fibrosis Bronchiectasis. It covers 8 dimensions: physical functioning, role functioning, emotional functioning, social functioning, vitality, treatment burden, health perceptions, and respiratory symptoms. Each dimension was scored separately on a scale of 0 to 100, and higher scores represent better outcomes. For this baseline measure, the respiratory symptoms domain score was reported.
[2]
Measure Analysis Population Description: Participants with data available for this measure at baseline.
Forced Expiratory Volume in One Second (FEV1)   [1] 
Mean (Standard Deviation)
Unit of measure:  Liter
Number Analyzed 141 participants 137 participants 70 participants 68 participants 416 participants
1.521  (0.521) 1.528  (0.625) 1.577  (0.651) 1.468  (0.574) 1.524  (0.587)
[1]
Measure Description: FEV1 was 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).
1.Primary Outcome
Title Time to First Exacerbation Event Within 48 Weeks
Hide Description Time to first exacerbation was defined as the time from randomization until the visit at which the first qualifying exacerbation is recorded by the investigator. Exacerbation events are defined as exacerbations with systemic antibiotic use and presence of fever or malaise / fatigue and worsening of at least three signs/symptoms.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included participants who were randomized.
Arm/Group Title Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Pooled Placebo
Hide Arm/Group Description:
Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).
Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).
Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day or 14-day on-treatment phase followed by a 28-day or 14-day off-treatment phase (48 weeks treatment phase = 6 or 12 cycles).
Overall Number of Participants Analyzed 141 137 138
Median (97.5% Confidence Interval)
Unit of Measure: Days
336 [1] 
(206 to NA)
NA [1] 
(290 to NA)
186
(136 to 282)
[1]
Value cannot be estimated due to censored data.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ciprofloxacin DPI 28 Days on/Off (Cipro 28), Pooled Placebo
Comments The hazard ratio for time to first exacerbation event within 48 weeks and 97.5% Confidence Interval (CI) was calculated by using Cox proportional hazards model by comparison of Cipro 28/Pooled Placebo reporting groups. P-value was analysed using Wald-type test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0650
Comments [Not Specified]
Method Wald-type test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.7331
Confidence Interval (2-Sided) 97.5%
0.5027 to 1.0690
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ciprofloxacin DPI 14 Days on/Off (Cipro 14), Pooled Placebo
Comments The hazard ratio for time to first exacerbation event within 48 weeks and 97.5% CI was calculated by using Cox proportional hazards model by comparison of Cipro 14/Pooled Placebo reporting groups. P-value was analysed using Wald-type test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Wald-type test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.5333
Confidence Interval (2-Sided) 97.5%
0.3568 to 0.7971
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks
Hide Description For this outcome measure, exacerbation events were defined as exacerbations with systemic antibiotic use and presence of fever or malaise / fatigue and worsening of at least three signs/symptoms over 48 weeks.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included participants who were randomized.
Arm/Group Title Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Pooled Placebo
Hide Arm/Group Description:
Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).
Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).
Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day or 14-day on-treatment phase followed by a 28-day or 14-day off-treatment phase (48 weeks treatment phase = 6 or 12 cycles).
Overall Number of Participants Analyzed 141 137 138
Measure Type: Number
Unit of Measure: Participants
Number of exacerbations: 0 66 72 44
Number of exacerbations: 1 44 38 58
Number of exacerbations: 2 12 13 19
Number of exacerbations: 3 12 8 7
Number of exacerbations: 4 3 3 8
Number of exacerbations: 5 1 2 0
Number of exacerbations: 6 0 0 1
Number of exacerbations: 7 3 1 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ciprofloxacin DPI 28 Days on/Off (Cipro 28), Pooled Placebo
Comments A Poisson regression with adjustment for over-/under dispersion was used to analyze the number of exacerbation events over 48 weeks and to test the difference in the frequency of exacerbation between Ciprofloxacin DPI 28 and Pooled placebo group. P-value was analyzed using Wald-type test along with the incidence rate ratio of the comparison.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2944
Comments [Not Specified]
Method Poisson regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence Rate Ratio
Estimated Value 0.8615
Confidence Interval (2-Sided) 97.5%
0.6264 to 1.1848
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ciprofloxacin DPI 14 Days on/Off (Cipro 14), Pooled Placebo
Comments A Poisson regression with adjustment for over-/under dispersion was used to analyze the number of exacerbation events over 48 weeks and to test the difference in the frequency of exacerbation between Ciprofloxacin DPI 14 and Pooled placebo group. P-value was analyzed using Wald-type test along with the incidence rate ratio of the comparison.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0382
Comments [Not Specified]
Method Poisson regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Incidence Rate Ratio
Estimated Value 0.7329
Confidence Interval (2-Sided) 97.5%
0.5237 to 1.0256
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks
Hide Description For this outcome measure, exacerbation events were defined as exacerbations with systemic antibiotic use and worsening of at least one sign/symptom over 48 weeks.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included participants who were randomized.
Arm/Group Title Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Pooled Placebo
Hide Arm/Group Description:
Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).
Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).
Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day or 14-day on-treatment phase followed by a 28-day or 14-day off-treatment phase (48 weeks treatment phase = 6 or 12 cycles).
Overall Number of Participants Analyzed 141 137 138
Measure Type: Number
Unit of Measure: Participants
Number of exacerbations: 0 58 68 46
Number of exacerbations: 1 47 42 43
Number of exacerbations: 2 12 15 31
Number of exacerbations: 3 14 5 11
Number of exacerbations: 4 4 2 5
Number of exacerbations: 5 4 3 2
Number of exacerbations: 6 2 2 0
4.Secondary Outcome
Title Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46)
Hide Description Pathogen eradication was defined as a negative culture result for all pre-specified pathogens at end of treatment (week 44 or 46 depending on treatment regimen) that were present in the participant at baseline. There was no imputation for participants who discontinued the study prematurely.
Time Frame End of treatment (Week 44/46)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included participants who were randomized.
Arm/Group Title Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Pooled Placebo
Hide Arm/Group Description:
Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).
Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).
Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day or 14-day on-treatment phase followed by a 28-day or 14-day off-treatment phase (48 weeks treatment phase = 6 or 12 cycles).
Overall Number of Participants Analyzed 141 137 138
Measure Type: Number
Unit of Measure: Percentage of Participants
No 39.0 26.3 33.3
Yes 24.1 28.5 16.7
5.Secondary Outcome
Title Mean Change From Baseline in Patient Reported Outcome Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score at End of Treatment (Week 44/46)
Hide Description The SGRQ was a validated, disease-specific instrument that measures health-related quality of life (HRQoL) in adults with chronic obstructive pulmonary disease (COPD) and asthma and was later validated for use in bronchiectasis. The SGRQ covers 3 dimensions: symptoms, activity and impact on daily life. To determine the outcome, a score ranging from 1 to 100 was calculated for each individual domain and for the total score, and smaller scores indicate better health status. For this outcome measure, the symptoms component score was reported.
Time Frame Baseline and end of treatment (Week 44/46)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with participants evaluable for this outcome measure.
Arm/Group Title Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Placebo 28 Days on/Off (Placebo 28) Placebo 14 Days on/Off (Placebo 14)
Hide Arm/Group Description:
Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).
Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).
Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 cycles).
Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 cycles).
Overall Number of Participants Analyzed 115 101 46 45
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-8.17  (22.92) -7.20  (20.41) -4.23  (19.55) 2.78  (16.16)
6.Secondary Outcome
Title Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46)
Hide Description New pathogens were any of the pre-specified organisms not cultured before start of study medication. There was no imputation for participants who discontinued the study prematurely.
Time Frame End of treatment (Week 44/46)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included participants who were randomized.
Arm/Group Title Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Pooled Placebo
Hide Arm/Group Description:
Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).
Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).
Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day or 14-day on-treatment phase followed by a 28-day or 14-day off-treatment phase (48 weeks treatment phase = 6 or 12 cycles).
Overall Number of Participants Analyzed 141 137 138
Measure Type: Number
Unit of Measure: Percentage of Participants
No 60.3 49.6 42.8
Yes 3.5 5.1 8.0
7.Secondary Outcome
Title Mean Change From Baseline in Patient Reported Outcome Quality of Life Questionnaire for Bronchiectasis (QoL-B) Respiratory Symptoms Domain Score at End of Treatment (Week 44/46)
Hide Description The QoL-B was a disease-specific questionnaire developed for non-Cystic fibrosis Bronchiectasis. It covers 8 dimensions: physical functioning, role functioning, emotional functioning, social functioning, vitality, treatment burden, health perceptions, and respiratory symptoms. Each dimension was scored separately on a scale of 0 to 100, and higher scores represent better outcomes. For this outcome measure, the respiratory symptoms domain score was reported.
Time Frame Baseline and end of treatment (Week 44/46)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with participants evaluable for this outcome measure.
Arm/Group Title Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Placebo 28 Days on/Off (Placebo 28) Placebo 14 Days on/Off (Placebo 14)
Hide Arm/Group Description:
Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).
Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).
Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 cycles).
Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 cycles).
Overall Number of Participants Analyzed 110 95 46 44
Mean (Standard Deviation)
Unit of Measure: Score on a scale
7.70  (18.50) 6.72  (17.90) 8.22  (16.74) 4.45  (17.78)
8.Secondary Outcome
Title Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at End of Treatment (Week 44/46)
Hide Description 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).
Time Frame Baseline and end of treatment (Week 44/46)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with participants evaluable for this outcome measure.
Arm/Group Title Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Placebo 28 Days on/Off (Placebo 28) Placebo 14 Days on/Off (Placebo 14)
Hide Arm/Group Description:
Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).
Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).
Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 cycles).
Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 cycles).
Overall Number of Participants Analyzed 112 98 45 41
Mean (Standard Deviation)
Unit of Measure: Liter
-0.012  (0.149) -0.026  (0.226) 0.024  (0.344) 0.022  (0.352)
Time Frame From start of study treatment up to 30 days after the last study drug administration.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Pooled Placebo
Hide Arm/Group Description Participants received ciprofloxacin (BAYQ3939) 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles). Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles). Participants received matching placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of either a 28-day days on-treatment phase followed by 28-day off-treatment phase or 14-day on-treatment phase followed by 14-day off treatment phase (48 weeks treatment phase = 6 cycles and 12 cycles, respectively).
All-Cause Mortality
Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Pooled Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Pooled Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   29/141 (20.57%)      23/136 (16.91%)      32/137 (23.36%)    
Blood and lymphatic system disorders       
Anaemia * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Cardiac disorders       
Atrial fibrillation * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Atrial flutter * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Cardiac failure * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 2/137 (1.46%)  2
Cardiac failure acute * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Cardiac failure congestive * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Cor pulmonale * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Mitral valve incompetence * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Eye disorders       
Angle closure glaucoma * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Retinal vasculitis * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Gastrointestinal disorders       
Ascites * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Gastric ulcer haemorrhage * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
General disorders       
Strangulated hernia * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Peripheral swelling * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
General physical health deterioration * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Hepatobiliary disorders       
Portal hypertension * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Immune system disorders       
Hypogammaglobulinaemia * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Infections and infestations       
Bronchiolitis * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Cellulitis * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 1/137 (0.73%)  1
Gastroenteritis clostridial * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Influenza * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Pathogen resistance * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Pneumonia * 1  4/141 (2.84%)  4 4/136 (2.94%)  4 5/137 (3.65%)  5
Urosepsis * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Infective exacerbation of bronchiectasis * 1  2/141 (1.42%)  3 1/136 (0.74%)  1 1/137 (0.73%)  1
Pyometra * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Injury, poisoning and procedural complications       
Clavicle fracture * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Complications of transplant surgery * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Femoral neck fracture * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Fibula fracture * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Urethral stricture traumatic * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Lumbar vertebral fracture * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Meniscus injury * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Investigations       
Influenza A virus test positive * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Metabolism and nutrition disorders       
Hyponatraemia * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Fracture nonunion * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Lumbar spinal stenosis * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Breast cancer * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Malignant melanoma * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Squamous cell carcinoma of skin * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Thyroid cancer recurrent * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Invasive lobular breast carcinoma * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Nervous system disorders       
Cerebral atrophy * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Cerebrovascular accident * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Normal pressure hydrocephalus * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Paraesthesia * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Syncope * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Transient global amnesia * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Renal and urinary disorders       
Haematuria * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Renal failure * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Urinary retention * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Urethral stenosis * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  2
Acute kidney injury * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Reproductive system and breast disorders       
Prostatic haemorrhage * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Bronchiectasis * 1  16/141 (11.35%)  20 8/136 (5.88%)  9 17/137 (12.41%)  19
Bronchospasm * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Dyspnoea * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Epistaxis * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Haemoptysis * 1  2/141 (1.42%)  2 1/136 (0.74%)  1 2/137 (1.46%)  2
Hypoxia * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Pleural effusion * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Pneumonia aspiration * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Pulmonary embolism * 1  1/141 (0.71%)  1 0/136 (0.00%)  0 0/137 (0.00%)  0
Pulmonary haemorrhage * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
Respiratory failure * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 1/137 (0.73%)  1
Vascular disorders       
Aortic stenosis * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Orthostatic hypotension * 1  0/141 (0.00%)  0 1/136 (0.74%)  1 0/137 (0.00%)  0
Deep vein thrombosis * 1  0/141 (0.00%)  0 0/136 (0.00%)  0 1/137 (0.73%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (18.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Pooled Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   74/141 (52.48%)      83/136 (61.03%)      62/137 (45.26%)    
Gastrointestinal disorders       
Diarrhoea * 1  7/141 (4.96%)  7 9/136 (6.62%)  11 5/137 (3.65%)  5
Nausea * 1  5/141 (3.55%)  5 10/136 (7.35%)  11 7/137 (5.11%)  7
General disorders       
Chest pain * 1  5/141 (3.55%)  5 7/136 (5.15%)  8 7/137 (5.11%)  7
Fatigue * 1  6/141 (4.26%)  6 12/136 (8.82%)  14 3/137 (2.19%)  3
Infections and infestations       
Nasopharyngitis * 1  15/141 (10.64%)  20 16/136 (11.76%)  21 10/137 (7.30%)  15
Sinusitis * 1  4/141 (2.84%)  5 10/136 (7.35%)  12 8/137 (5.84%)  10
Upper respiratory tract infection * 1  4/141 (2.84%)  5 9/136 (6.62%)  9 10/137 (7.30%)  13
Investigations       
Aspergillus test positive * 1  6/141 (4.26%)  6 7/136 (5.15%)  8 0/137 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Back pain * 1  10/141 (7.09%)  13 9/136 (6.62%)  10 6/137 (4.38%)  6
Nervous system disorders       
Dizziness * 1  2/141 (1.42%)  2 7/136 (5.15%)  7 1/137 (0.73%)  1
Headache * 1  11/141 (7.80%)  14 14/136 (10.29%)  16 4/137 (2.92%)  6
Respiratory, thoracic and mediastinal disorders       
Bronchospasm * 1  6/141 (4.26%)  7 7/136 (5.15%)  13 10/137 (7.30%)  13
Cough * 1  15/141 (10.64%)  18 13/136 (9.56%)  18 9/137 (6.57%)  12
Dyspnoea * 1  15/141 (10.64%)  21 16/136 (11.76%)  26 9/137 (6.57%)  11
Haemoptysis * 1  15/141 (10.64%)  34 16/136 (11.76%)  32 8/137 (5.84%)  10
Sputum increased * 1  8/141 (5.67%)  9 6/136 (4.41%)  8 3/137 (2.19%)  4
Oropharyngeal pain * 1  3/141 (2.13%)  3 7/136 (5.15%)  9 5/137 (3.65%)  5
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (18.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Bayer acknowledges and accepts the interest in the noncommercial scientific publication of Results. In a multicenter study the PIs will not make any publication of the results before the first multi-center publication. Proposed publication/presentation shall be provided to Bayer at least 60 days prior to the intended submission or presentation of the publication in order to allow Bayer to review it. Any difference of opinion shall be discussed.
Results Point of Contact
Name/Title: Therapeutic Area Head
Organization: BAYER
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01764841     History of Changes
Other Study ID Numbers: 15625
2011-004208-39 ( EudraCT Number )
First Submitted: January 8, 2013
First Posted: January 10, 2013
Results First Submitted: February 22, 2017
Results First Posted: May 24, 2017
Last Update Posted: January 24, 2018