Non-Cystic Fibrosis Bronchiectasis

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.

BAY q 3939 / Ciprofloxacin hydrated capsule 32.5 mg for inhalation

Ciprofloxacin

capsule for inhalation

32.5 mg

The primary objectives of this study are:
- To evaluate the efficacy of ciprofloxacin DPI administered BID intermittently for 28 days on study treatment / 28 days off study treatment or 14 days on study treatment/ 14 days off study treatment to prolong the time to first exacerbation requiring an intervention with systemic antibiotics in subjects with non-CF BE (as agreed with the US FDA(Food and Drug Administration)).
- To evaluate the efficacy of ciprofloxacin dry powder for inhalation (DPI) administered 2 times a day (BID) intermittently for 28 days on study treatment / 28 days off study treatment or 14 days on study treatment / 14 days off study treatment in reducing the frequency of pulmonary exacerbation requiring an intervention with systemic antibiotics in subjects with non–CF BE (as agreed with the EMA (European Medical Agency) /CHMP) within 48 weeks after start of treatment.

The secondary objectives of this study are:
- To assess pathogen eradication and acquisition of new pathogenic organisms not present at baseline;
- To assess the safety and tolerability of different long term regimen of ciprofloxacin
DPI;
- To assess the improvement of quality of life by Saint George’s Respiratory Questionnaire (SGRQ);
- To assess changes in lung function as measured by change in FEV1.
Further objectives are:
- To assess the quality of life by Quality of Life-Bronchiectasis (QOL-B) questionnaire;
- To assess the inflammatory response measured by the following inflammatory markers: high-sensitivity C-reactive protein (hsCRP), polymorphonuclear leukocytes(PMNs), interleukin-8 (IL-8), and myeloperoxidase (MPO).
- To assess the selection of resistant isolates in the different treatment groups.

[Inclusion criteria]
1) Age >= 18 years;
2) Proven and documented diagnosis of non-CF idiopathic or post-infectious BE by CT scan (conventional high resolution CT is considered the standard) including 2 or more lobes and dilated airways compatible with BE at initial diagnosis
3) Positive culture from an adequate sputum sample for Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Streptococcus
pneumoniae, Stenotrophomonas maltophilia or Burkholderia cepacia at screening and with history ≥2 documented exacerbations in the past 12 months.
4) Stable pulmonary status as indicated by FEV1 (percent of predicted) >=30% and <90% (post-bronchodilator, if used as standard of treatment);
5) Stable regimen of standard treatment with:
- Bronchodilators, anticholinergics, inhaled corticosteroids, or mucolytics, if used as chronic treatment for BE, at least for the past 4 weeks prior to screening.Subjects on maintenance therapy with low-dose systemic corticosteroids should be receiving 10 mg/day prednisolone equivalent at least for the past 4 weeks before the screening visit;
and/or
- Macrolides if used as chronic treatment for BE for at least 6 months prior to screening.
6) Sputum production on the majority of days;
7) Ability to follow the inhaler device instructions;
8) Ability to complete questionnaires;
9) Written informed consent;
10) Negative urine pregnancy test result for women of childbearing potential before
first dose of study drug;
11) Women of childbearing potential and men must agree to use adequate contraception when sexually active. This applies from the time of signing of the informed consent form (ICF) until 3 months after the last study drug administration. Adequate methods of contraception include vasectomy, or condom use, diaphragm
with spermicidal gel, coil (intrauterine device), surgical sterilization, or oral contraceptives.

[Exclusion criteria]
1) FEV1 <30% or >=90% predicted (post-bronchodilator);
2) Active allergic bronchopulmonary aspergillosis (ABPA);
3) Active and actively-treated non-tuberculosis mycobacterial (NTM) infection or tuberculosis;
4) Diagnosis of common variable immunodeficiency (CVID);
5) Recent significant hemoptysis (300 mL or requiring blood transfusion) in the preceding 4 weeks before screening (and during the screening period);
6) Primary diagnosis of COPD;
7) Known CF and / or documented chronic bronchial asthma;
8) Administration of any investigational drug within 4 weeks before screening;
9) Medical history of allergies to quinolones or fluoroquinolones;
10) Women who are pregnant, lactating, or in whom pregnancy cannot be excluded;
11) History of tendon disorders related to quinolone treatment;
12) History of myasthenia gravis;
13) Concomitant administration of tizanidine while on study drug;
14) Systemic or inhaled antibiotic treatment for any indication within 4 weeks prior to the administration of study drug; except for chronic macrolide use (see section 6.9).
15) Systemic corticosteroids at >10 mg/day prednisolone equivalent for >14 days within 4 weeks prior to the administration of study drug; (see section 6.9).
16) Participation in other investigational interventional studies within 4 weeks before screening;
17) Subjects with any other conditions (specifically those which are addressed in the warnings and precautions section of the IB) or clinically relevant laboratory findings that the investigator defines as not appropriate for enrollment of a subject into the study
18) Previous assignment to treatment in this study (randomized in Study 15626).