Evaluation of Cipro Inhale in Patients With Non-cystic Fibrosis Bronchiectasis

Randomized, Placebo-controlled, Double-blind, Multi-center Study to Evaluate the Safety and Efficacy of Ciprofloxacin Inhale Compared to Placebo in Patients With Non-cystic Fibrosis Bronchiectasis

The purpose of this study is to find out if bacterial load in the airways can be reduced after inhalation of ciprofloxacin for 28 days.

Study Overview

• Status: Completed
• Conditions: Bronchiectasis
• Intervention / Treatment: Drug: Ciprofloxacin (Cipro, BAYQ3939); Drug: Placebo

Detailed Description

Safety issues are addressed in the AE section. There is no standardised and unanimously accepted definition of exacerbation in COPD; 4 definitions are widely used: (1) using a combination of 3 cardinal symptoms: increased dyspnea, sputum volume, and sputum purulence; (2) looking at the presence of the following patterns of symptoms during >=2 consecutive days: either 2 or more of 3 major symptoms (increase in dyspnoea, sputum volume and sputum purulence); or any 1 major symptom together with any 1 minor symptom (increase in nasal discharge, wheeze, sore throat, cough or fever); (3) a sustained worsening of the patient's condition, from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitates a change in regular medication in a patient with underlying COPD; (4) a complex of respiratory events (i.e. cough, wheezing, dyspnoea or sputum production) lasting >=3 days.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
    • Woollongabba, Queensland, Australia, 4102
  • South Australia
    • Adelaide, South Australia, Australia, 5000
    • Adelaide, South Australia, Australia, 5065
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
    • Prahran, Victoria, Australia, 3181
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
• Germany
  • Berlin, Germany, 14059
  • Berlin, Germany, 12203
  • Berlin, Germany, 10961
  • Berlin, Germany, 13507
  • Baden-Württemberg
    • Löwenstein, Baden-Württemberg, Germany, 74245
  • Brandenburg
    • Rüdersdorf, Brandenburg, Germany, 15562
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
    • Gelnhausen, Hessen, Germany, 63571
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
    • Hannover, Niedersachsen, Germany, 30167
  • Nordrhein-Westfalen
    • Witten, Nordrhein-Westfalen, Germany, 58452
  • Rheinland-Pfalz
    • Koblenz, Rheinland-Pfalz, Germany, 56068
    • Mainz, Rheinland-Pfalz, Germany, 55131
  • Schleswig-Holstein
    • Geesthacht, Schleswig-Holstein, Germany, 21502
    • Großhansdorf, Schleswig-Holstein, Germany, 22927
  • Thüringen
    • Bad Berka, Thüringen, Germany, 99437
• Spain
  • Badajoz, Spain, 06080
  • Barcelona, Spain, 08036
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
  • Illes Baleares
    • Palma de Mallorca, Illes Baleares, Spain, 07010
• Sweden
  • Uppsala, Sweden, 751 85
• United Kingdom
  • Edinburgh, United Kingdom, EH16 4SA
  • Norwich, United Kingdom, NR4 7UY
  • Avon
    • Bristol, Avon, United Kingdom, BS2 8HW
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB3 8RE
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L9 7JU
  • North Ireland
    • Belfast, North Ireland, United Kingdom, BT12 7AB
  • Tyne and Wear
    • Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • California
    • La Jolla, California, United States, 92037
  • Colorado
    • Denver, Colorado, United States, 80206
  • Connecticut
    • Farmington, Connecticut, United States, 06030
  • District of Columbia
    • Washington, District of Columbia, United States, 20007-2197
  • Florida
    • Naples, Florida, United States, 34109-0446
  • Indiana
    • Michigan City, Indiana, United States, 46360
  • New York
    • Mineola, New York, United States, 11501
  • Texas
    • Houston, Texas, United States, 77204
    • Tyler, Texas, United States, 75708-3154
  • Utah
    • Payson, Utah, United States, 84651

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a proven and documented diagnosis of non-cystic fibrosis idiopathic or post pneumonic bronchiectasis
• Stable pulmonary status and stable regimen of standard treatment at least for the past 30 days

Exclusion Criteria:

• Forced Expiratory Volume 1 < 35% or > 80%
• Allergic bronchopulmonary aspergillosis
• Immunodeficiency disease requiring immunoglobulin replacement
• Inflammatory bowel disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ciprofloxacin Inhale (BAYQ3939); 32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily	Drug: Ciprofloxacin (Cipro, BAYQ3939); Inhalation of 32,5mg Ciprofloxacin inhaled twice a day
Placebo Comparator: Placebo; Inhalation of matching placebo twice a day	Drug: Placebo; Inhalation of matching placebo twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Bacterial Load in the Sputum at End of Treatment (Day 29).	Total bacterial load was determined in sputum collected before the inhalation of study drug. Sputum samples were either provided by the participant during the respective study visit, or participants had to bring a sputum sample that had been produced within the 4 hours prior to the visit. Induced sputum samples could be collected if the participant was unable to produce a spontaneously expectorated sputum sample of > 2 mL. Imputation method: last observation carried forward (LOCF). CFU: colony forming units, log10: decadic logarithm	Baseline and 29 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)	Pulmonary function testing (spirometry) was conducted in accordance with American Thoracic Society standards. 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). Imputation method: last observation carried forward (LOCF).	Baseline and up to end of study (planned at Day 84)
Change From Baseline in Forced Vital Capacity (FVC)	Pulmonary function testing (spirometry) was conducted in accordance with American Thoracic Society standards. FVC was defined as the maximal volume of air exhaled with maximally forced effort from a maximal inspiration, i.e. vital capacity performed with a maximally forced expiratory effort expressed in liters at BTPS. Imputation method: last observation carried forward (LOCF).	Baseline and up to end of study (planned at Day 84)
Time to Exacerbation With Antibiotic Intervention	Acute exacerbation was defined according to the joint American Thoracic Society/European Respiratory Society criteria. For detailed information with regard to this definition of acute exacerbation, please refer to the detailed description in the protocol section. The time to an acute exacerbation with antibiotic intervention was determined.	Up to end of study (planned at Day 84)
Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score	Participants completed the Saint George's Respiratory Questionnaire (SGRQ). They were assured that all data would be treated confidentially and that the answers would not have any influence on study drug treatment. Participants completed the questionnaires on their own in a quiet area, without discussing them with study staff or accompanying persons (e.g. friends or relatives) and before being seen by the clinician. The score ranges from 0 to 100 with 100 being the worst possible score.	Up to end of study (planned at Day 84)
Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS)	Participants completed the Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS). They were assured that all data would be treated confidentially and that the answers would not have any influence on study drug treatment. Participants completed the questionnaires on their own in a quiet area, without discussing them with study staff or accompanying persons (e.g. friends or relatives) and before being seen by the clinician. The score ranges between 1 and 7, 1 being the worst possible score.	Up to end of study (planned at Day 84)
Change From Baseline in High Sensitive C-reactive Protein (hsCRP)	High sensitive C-reactive protein (hsCRP) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available.	Baseline and up to Day 42
Change From Baseline in Absolute Neutrophil Count (ANC)	Absolute neutrophil count (ANC) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available.	Baseline and up to Day 42
24-hour Sputum Volume	Participants were asked to start 24-hour sputum collection samples 24 hours before coming for the respective study visit. The volume of the completed sample was determined.	Up to end of study (planned at Day 84)
24-hour Sputum Color (Percentage of Participants With Non-clear Sputum)	Participants were asked to start 24-hour sputum collection samples 24 hours before coming for the respective study visit. Sputum color was assessed as either 'clear', or as 'yellow', 'green' or 'rust', or an assessment of 'no sputum' was made.	Up to end of study (planned at Day 84)
Microbiological Response of Cipro Inhale Per Participant	Microbiological response was defined as reduction in bacterial load or eradication (measured as the percentage of participants with positive culture). Missing values were not imputed.	Up to end of study (planned at Day 84)
Microbiological Response of Cipro Inhale Per Pathogen	Microbiological response was defined as reduction in bacterial load or eradication (measured as the number of participants with positive culture). Missing values were not imputed. Pathogens analyzed: Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Serratia marcescens, Pseudomonas aeruginosa, mucoid, Pseudomonas aeruginosa, non mucoid, Stenotrophomonas maltophilia, Achromobacter xylosoxydans, Moraxella catarrhalis, Haemophilus influenzae	Up to end of study (planned at Day 84)
Emergence of New Potential Respiratory Pathogens	The emergence of new potential respiratory pathogens was evaluated using microbiological analysis. Evaluated was the cumulative number of participants with first appearance of new potential respiratory antigens at each time point. In some cases, participants attended the end of study visit later than Day 84 (up to Day 88).	Up to end of study (planned at Day 84)
Emergence of Resistance Among Baseline Pathogens	The emergence of resistance (at least two-fold increase of Minimal inhibitory concentration, MIC, vs. baseline values) probably or possibly related to study medication among baseline pathogens was evaluated using microbiological analysis.	Up to end of study (planned at Day 84)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Bacterial Load in the Sputum	Total bacterial load was determined in sputum collected before the inhalation of study drug. Sputum samples were either provided by the participant during the respective study visit, or participants had to bring a sputum sample that had been produced within the 4 hours prior to the visit. Induced sputum samples could be collected if the participant was unable to produce a spontaneously expectorated sputum sample of > 2 mL on Day 8. Imputation method: last observation carried forward (LOCF). CFU: colony forming units, log10: decadic logarithm	Baseline and up to end of study (planned at Day 84)

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Novartis

Publications and helpful links

General Publications

• Wilson R, Welte T, Polverino E, De Soyza A, Greville H, O'Donnell A, Alder J, Reimnitz P, Hampel B. Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis: a phase II randomised study. Eur Respir J. 2013 May;41(5):1107-15. doi: 10.1183/09031936.00071312. Epub 2012 Sep 27.

Helpful Links

• Click here and search for Bayer products information provided by EMA

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: June 30, 2009
• First Submitted That Met QC Criteria: June 30, 2009
• First Posted (Estimate): July 2, 2009

Study Record Updates

• Last Update Posted (Estimate): December 12, 2014
• Last Update Submitted That Met QC Criteria: November 28, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Bronchiectasis; Ciprofloxacin; Airway infection
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Ciprofloxacin
• Other Study ID Numbers: 12965; 2009-009869-34 (EudraCT Number)