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.
Interventions
DRUGCiprofloxacin (BAYQ3939) dry powder for inhalation
Ciprofloxacin dry powder for inhalation (DPI) 32.5 mg inhaled twice daily in cycles of 28 days on-treatment and 28 days off-treatment.
DRUGPlacebo
Matching placebo inhaled twice daily intermittently for 28 days on / 28 days off
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 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 - Cipro 28 vs. Pooled Placebo | 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. |
| Time to First Exacerbation Event Within 48 Weeks - Cipro 14 vs. Pooled Placebo | 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 |
|---|---|---|
| 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. |
| 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. |
Countries
Argentina, Australia, Austria, Brazil, Bulgaria, China, Czechia, Germany, Hong Kong, Latvia, Lithuania, Netherlands, Philippines, Poland, Portugal, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Taiwan, Thailand, Turkey (Türkiye), United States
Participant flow
Recruitment details
Study was conducted at 164 study centers in 25 countries between 30 April 2014 (first subject first visit) and 19 October 2016 (last subject last visit).
Pre-assignment details
A total of 1123 subjects were screened and 521 subjects were randomized. The randomized subjects were allocated to treatment groups, and 2 subjects in the Cipro 14 group did not receive study medication.
Participants by arm
| Arm | Count |
|---|---|
| Ciprofloxacin DPI 28 Days on/Off (Cipro 28) Subjects 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). | 171 |
| Ciprofloxacin DPI 14 Days on/Off (Cipro 14) Subjects 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). | 176 |
| Placebo 28 Days on/Off (Placebo 28) Subjects 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). | 86 |
| Placebo 14 Days on/Off (Placebo 14) Subjects 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). | 88 |
| Total | 521 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 3 | 0 |
| Overall Study | Death | 4 | 4 | 1 | 4 |
| Overall Study | Deterioration of general conditions | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 3 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 |
| Overall Study | Technical problems | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 17 | 17 | 10 | 7 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|
| Age, Continuous | 59.3 Years STANDARD_DEVIATION 14.2 | 60.4 Years STANDARD_DEVIATION 13.7 | 60.6 Years STANDARD_DEVIATION 13.7 | 60.4 Years STANDARD_DEVIATION 15 | 60.1 Years STANDARD_DEVIATION 14 |
| Forced Expiratory Volume in One Second (FEV1) | 1.569 Liter STANDARD_DEVIATION 0.602 | 1.519 Liter STANDARD_DEVIATION 0.617 | 1.560 Liter STANDARD_DEVIATION 0.692 | 1.477 Liter STANDARD_DEVIATION 0.558 | 1.535 Liter STANDARD_DEVIATION 0.615 |
| Quality of Life Questionnaire for Bronchiectasis (QoL-B) Respiratory Symptoms Domain Score | 50.14 Score on a scale STANDARD_DEVIATION 19.07 | 52.17 Score on a scale STANDARD_DEVIATION 18.49 | 53.95 Score on a scale STANDARD_DEVIATION 16 | 48.67 Score on a scale STANDARD_DEVIATION 17.72 | 51.22 Score on a scale STANDARD_DEVIATION 18.16 |
| Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score | 60.75 Score on a scale STANDARD_DEVIATION 20.61 | 61.26 Score on a scale STANDARD_DEVIATION 19.54 | 58.56 Score on a scale STANDARD_DEVIATION 19.17 | 63.47 Score on a scale STANDARD_DEVIATION 19.48 | 61.00 Score on a scale STANDARD_DEVIATION 19.82 |
| Sex: Female, Male Female | 92 Participants | 96 Participants | 52 Participants | 62 Participants | 302 Participants |
| Sex: Female, Male Male | 79 Participants | 80 Participants | 34 Participants | 26 Participants | 219 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 | 51 / 171 | 60 / 174 | 55 / 174 |
| serious Total, serious adverse events | 28 / 171 | 45 / 174 | 41 / 174 |
Outcome results
Primary
Time to First Exacerbation Event Within 48 Weeks - Cipro 14 vs. Pooled Placebo
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 - Cipro 14 vs. Pooled Placebo | NA Days |
| Pooled Placebo | Time to First Exacerbation Event Within 48 Weeks - Cipro 14 vs. Pooled Placebo | NA Days |
Comparison: The hazard ratio for time to first exacerbation event within 48 weeks and 95.1% 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: 0.396595.1% CI: [0.6206, 1.209]Wald-type test
Primary
Time to First Exacerbation Event Within 48 Weeks - Cipro 28 vs. Pooled Placebo
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 - Cipro 28 vs. Pooled Placebo | NA Days |
| Pooled Placebo | Time to First Exacerbation Event Within 48 Weeks - Cipro 28 vs. Pooled Placebo | NA Days |
Comparison: The hazard ratio for time to first exacerbation event within 48 weeks and 99.9% 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: 0.051199.9% CI: [0.3928, 1.2698]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) | 0.038 Liter | Standard Deviation 0.336 |
| Pooled Placebo | Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at End of Treatment (Week 44/46) | -0.037 Liter | Standard Deviation 0.287 |
| Pooled Placebo | Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at End of Treatment (Week 44/46) | -0.038 Liter | Standard Deviation 0.272 |
| 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) | 0.037 Liter | Standard Deviation 0.299 |
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) | 11.57 Score on a scale | Standard Deviation 17.49 |
| 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) | 10.90 Score on a scale | Standard Deviation 18.07 |
| 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) | 7.08 Score on a scale | Standard Deviation 17 |
| 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) | 10.70 Score on a scale | Standard Deviation 15.58 |
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) | -8.92 Score on a scale | Standard Deviation 21.06 |
| 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) | -9.02 Score on a scale | Standard Deviation 20.1 |
| 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) | -2.91 Score on a scale | Standard Deviation 24.48 |
| 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) | -11.50 Score on a scale | Standard Deviation 18.54 |
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 (COUNT_OF_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 | 102 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: 1 | 51 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 | 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: 3 | 3 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 | 1 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 | 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 | 1 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 0 | 96 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 3 | 4 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 4 | 3 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 1 | 46 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 2 | 26 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 1 | 45 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 2 | 22 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: 0 | 90 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks | Number of exacerbations: 4 | 4 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 (COUNT_OF_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 | 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: 2 | 8 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 | 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: 3 | 2 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 | 46 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 | 115 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 | 108 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 1 | 40 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 2 | 23 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 3 | 4 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 4 | 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 | 10 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 1 | 41 Participants |
| Pooled Placebo | Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks | Number of exacerbations: 5 | 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 | 2 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: 0 | 101 Participants |
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 | 62.6 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 | 4.1 Percentage of participants |
| Pooled Placebo | Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46) | No | 67.6 Percentage of participants |
| Pooled Placebo | Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46) | Yes | 4.0 Percentage of participants |
| Pooled Placebo | Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46) | No | 61.5 Percentage of participants |
| Pooled Placebo | Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46) | Yes | 10.3 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 | 35.1 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 | 31.6 Percentage of participants |
| Pooled Placebo | Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46) | No | 35.8 Percentage of participants |
| Pooled Placebo | Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46) | Yes | 35.8 Percentage of participants |
| Pooled Placebo | Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46) | No | 40.2 Percentage of participants |
| Pooled Placebo | Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46) | Yes | 31.6 Percentage of participants |