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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized, Double-blind, Placebo-controlled, Multicenter Study Comparing Ciprofloxacin DPI 32.5 mg BID (Twice a Day) Intermittently Administered for 28 Days on / 28 Days Off or 14 Days on / 14 Days Off Versus Placebo to Evaluate the Time to First Pulmonary Exacerbation and Frequency of Exacerbations in Subjects With Non-Cystic Fibrosis Bronchiectasis.

Conditions
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Bronchiectasis

Intervention / Treatment
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* Drug: Ciprofloxacin DPI (BAYQ3939)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ciprofloxacin DPI 28 Days on/off (Cipro 28)<br>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). | Drug: Ciprofloxacin DPI (BAYQ3939)<br>* Participants received 32.5 mg ciprofloxacin hydrated (corresponding to 50 mg dry powder) administered BID (every 12 hours) using T-326 powder inhaler device.<br>|
| Experimental: Ciprofloxacin DPI 14 Days on/off (Cipro 14)<br>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). | Drug: Ciprofloxacin DPI (BAYQ3939)<br>* Participants received 32.5 mg ciprofloxacin hydrated (corresponding to 50 mg dry powder) administered BID (every 12 hours) using T-326 powder inhaler device.<br>|
| Placebo Comparator: Placebo 28 Days on/off (Placebo 28)<br>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). | Drug: Placebo<br>* 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.<br>|
| Placebo Comparator: Placebo 14 Days on/off (Placebo 14)<br>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). | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to Week 48 | 
| 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. | Up to Week 48 | 
| 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. | End of treatment (Week 44/46) | 
| 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. | Baseline and end of treatment (Week 44/46) | 
| 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. | End of treatment (Week 44/46) | 
| 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. | Baseline and end of treatment (Week 44/46) | 
| 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). | Baseline and end of treatment (Week 44/46) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ciprofloxacin, Dry Powder for Inhalation, Exacerbation, Bronchiectasis