Bronchiectasis
Conditions
Keywords
Ciprofloxacin, Dry Powder for Inhalation, Exacerbation, Bronchiectasis
Brief summary
The purpose of this study is to evaluate if the time to first pulmonary exacerbation of bronchiectasis or its frequency can be prolonged by inhalation of ciprofloxacin for 28 days every other 28 days or for 14 days every other 14 days over 48 weeks.
Detailed description
Number of participants with Adverse events will be covered in Adverse Events section. The statistical analysis tests for the efficacy variables will be performed hierarchically. The comparisons ciprofloxacin DPI vs. pooled placebo (according to statistical analysis plan defined for FDA registration) will be performed in parallel for the regimen 28 days on/off and 14 days on/off.
Interventions
DRUGCiprofloxacin DPI (BAYQ3939)
Participants received 32.5 mg ciprofloxacin hydrated (corresponding to 50 mg dry powder) administered BID (every 12 hours) using T-326 powder inhaler device.
DRUGPlacebo
Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours) using T-326 powder inhaler device.
Sponsors
Novartis
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a proven and documented diagnosis of non Cystic Fibrosis (CF) idiopathic or post infectious bronchiectasis * Stable pulmonary status and stable regimen of standard treatment at least for the past 4 weeks
Exclusion criteria
* Forced expiratory volume in 1 second (FEV1) \<30% or \>90% predicted * Active allergic bronchopulmonary aspergillosis * Active and actively treated non tuberculosis mycobacterial (NTM) infection or tuberculosis * Primary diagnosis of Chronic obstructive pulmonary disease (COPD)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Exacerbation Event Within 48 Weeks | Up to Week 48 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Up to Week 48 | 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. |
| Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46) | End of treatment (Week 44/46) | 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. |
| Mean Change From Baseline in Patient Reported Outcome Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score at End of Treatment (Week 44/46) | Baseline and end of treatment (Week 44/46) | 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. |
| Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Up to Week 48 | 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. |
| 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) | Baseline and end of treatment (Week 44/46) | 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. |
| Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at End of Treatment (Week 44/46) | Baseline and end of treatment (Week 44/46) | 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). |
| Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46) | End of treatment (Week 44/46) | 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. |
Countries
Argentina, Australia, Denmark, France, Germany, Israel, Italy, Japan, Latvia, New Zealand, Slovakia, Spain, United Kingdom, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) 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). | 141 |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) 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). | 137 |
| Placebo 28 Days on/Off (Placebo 28) 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). | 70 |
| Placebo 14 Days on/Off (Placebo 14) 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). | 68 |
| Total | 416 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 3 | 0 | 1 | 4 |
| Overall Study | Logistical Difficulties | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 | 1 | 0 |
| Overall Study | No Follow Up | 1 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 16 | 24 | 11 | 15 |
Baseline characteristics
| Characteristic | Total | 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) |
|---|---|---|---|---|---|
| Age, Continuous | 64.7 Years STANDARD_DEVIATION 12.9 | 64.2 Years STANDARD_DEVIATION 12.1 | 65.2 Years STANDARD_DEVIATION 13.5 | 64 Years STANDARD_DEVIATION 13.5 | 65.5 Years STANDARD_DEVIATION 12.9 |
| Forced Expiratory Volume in One Second (FEV1) | 1.524 Liter STANDARD_DEVIATION 0.587 | 1.521 Liter STANDARD_DEVIATION 0.521 | 1.528 Liter STANDARD_DEVIATION 0.625 | 1.577 Liter STANDARD_DEVIATION 0.651 | 1.468 Liter STANDARD_DEVIATION 0.574 |
| Quality of Life Questionnaire for Bronchiectasis (QoL-B) Respiratory Symptoms Domain Score | 54.57 Score on a scale STANDARD_DEVIATION 18.87 | 53.01 Score on a scale STANDARD_DEVIATION 18.71 | 57.69 Score on a scale STANDARD_DEVIATION 18.72 | 55.82 Score on a scale STANDARD_DEVIATION 18.04 | 50.67 Score on a scale STANDARD_DEVIATION 19.59 |
| Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score | 56.84 Score on a scale STANDARD_DEVIATION 20.95 | 60.72 Score on a scale STANDARD_DEVIATION 19.47 | 52.51 Score on a scale STANDARD_DEVIATION 21.48 | 55.52 Score on a scale STANDARD_DEVIATION 22.07 | 58.72 Score on a scale STANDARD_DEVIATION 20.4 |
| Sex: Female, Male Female | 285 Participants | 101 Participants | 88 Participants | 52 Participants | 44 Participants |
| Sex: Female, Male Male | 131 Participants | 40 Participants | 49 Participants | 18 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 74 / 141 | 83 / 136 | 62 / 137 |
| serious Total, serious adverse events | 29 / 141 | 23 / 136 | 32 / 137 |
Outcome results
Primary
Time to First Exacerbation Event Within 48 Weeks
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
Population: Full analysis set (FAS) included participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Time to First Exacerbation Event Within 48 Weeks | 336 Days |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Time to First Exacerbation Event Within 48 Weeks | NA Days |
| Pooled Placebo | Time to First Exacerbation Event Within 48 Weeks | 186 Days |
Comparison: 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.p-value: 0.06597.5% CI: [0.5027, 1.069]Wald-type test
Comparison: 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.p-value: 0.000597.5% CI: [0.3568, 0.7971]Wald-type test
Secondary
Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at End of Treatment (Week 44/46)
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)
Population: FAS with participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at End of Treatment (Week 44/46) | -0.012 Liter | Standard Deviation 0.149 |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at End of Treatment (Week 44/46) | -0.026 Liter | Standard Deviation 0.226 |
| Pooled Placebo | Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at End of Treatment (Week 44/46) | 0.024 Liter | Standard Deviation 0.344 |
| Placebo 14 Days on/Off (Placebo 14) | Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at End of Treatment (Week 44/46) | 0.022 Liter | Standard Deviation 0.352 |
Secondary
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)
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)
Population: FAS with participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | 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) | 7.70 Score on a scale | Standard Deviation 18.5 |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | 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) | 6.72 Score on a scale | Standard Deviation 17.9 |
| Pooled Placebo | 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) | 8.22 Score on a scale | Standard Deviation 16.74 |
| Placebo 14 Days on/Off (Placebo 14) | 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) | 4.45 Score on a scale | Standard Deviation 17.78 |
Secondary
Mean Change From Baseline in Patient Reported Outcome Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score at End of Treatment (Week 44/46)
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)
Population: FAS with participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Mean Change From Baseline in Patient Reported Outcome Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score at End of Treatment (Week 44/46) | -8.17 Score on a scale | Standard Deviation 22.92 |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Mean Change From Baseline in Patient Reported Outcome Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score at End of Treatment (Week 44/46) | -7.20 Score on a scale | Standard Deviation 20.41 |
| Pooled Placebo | Mean Change From Baseline in Patient Reported Outcome Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score at End of Treatment (Week 44/46) | -4.23 Score on a scale | Standard Deviation 19.55 |
| Placebo 14 Days on/Off (Placebo 14) | Mean Change From Baseline in Patient Reported Outcome Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score at End of Treatment (Week 44/46) | 2.78 Score on a scale | Standard Deviation 16.16 |
Secondary
Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks
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
Population: Full analysis set (FAS) included participants who were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 1 | 47 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 4 | 4 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 3 | 14 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 0 | 58 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 6 | 2 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 5 | 4 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 2 | 12 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 3 | 5 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 0 | 68 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 1 | 42 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 2 | 15 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 4 | 2 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 5 | 3 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 6 | 2 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 4 | 5 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 1 | 43 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 6 | 0 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 5 | 2 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 3 | 11 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 2 | 31 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 0 | 46 Participants |
Secondary
Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks
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
Population: Full analysis set (FAS) included participants who were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 2 | 12 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 7 | 3 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 4 | 3 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 3 | 12 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 6 | 0 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 1 | 44 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 0 | 66 Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 5 | 1 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 4 | 3 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 0 | 72 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 1 | 38 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 2 | 13 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 3 | 8 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 5 | 2 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 6 | 0 Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 7 | 1 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 4 | 8 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 5 | 0 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 0 | 44 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 7 | 1 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 6 | 1 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 3 | 7 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 2 | 19 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 1 | 58 Participants |
Comparison: 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.p-value: 0.294497.5% CI: [0.6264, 1.1848]Poisson regression
Comparison: 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.p-value: 0.038297.5% CI: [0.5237, 1.0256]Poisson regression
Secondary
Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46)
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)
Population: Full analysis set (FAS) included participants who were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46) | No | 60.3 Percentage of Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46) | Yes | 3.5 Percentage of Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46) | No | 49.6 Percentage of Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46) | Yes | 5.1 Percentage of Participants |
| Pooled Placebo | Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46) | No | 42.8 Percentage of Participants |
| Pooled Placebo | Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46) | Yes | 8.0 Percentage of Participants |
Secondary
Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46)
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)
Population: Full analysis set (FAS) included participants who were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46) | No | 39.0 Percentage of Participants |
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) | Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46) | Yes | 24.1 Percentage of Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46) | No | 26.3 Percentage of Participants |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) | Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46) | Yes | 28.5 Percentage of Participants |
| Pooled Placebo | Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46) | No | 33.3 Percentage of Participants |
| Pooled Placebo | Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46) | Yes | 16.7 Percentage of Participants |