Study to Evaluate the Safety and Pharmacokinetics of Inhaled Ciprofloxacin in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
=================
Brief Summary
-----------------
Objectives of the study are to investigate the safety, tolerability and levels of ciprofloxacin in the lung after single and multiple inhalative administration to patients with moderate to severe COPD (stage II-III according to GOLD Criteria)

Official Title
-----------------
Randomized, Single-Blinded, Placebo-Controlled Study to Evaluate the Safety and Tolerability, the Pulmonary Deposition and Pharmacokinetics of Ciprofloxacin in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (GOLD II - III), Following Inhalation of Ciprofloxacin PulmoSphere® Inhalation Powder

Conditions
-----------------
Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
-----------------
* Drug: Ciprofloxacin (PulmoSphere, BAYQ3939)
* Drug: Ciprofloxacin (PulmoSphere, BAYQ3939)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult patients with COPD, 40 to 75 years of age Diagnosis of COPD Airway obstruction with a post-bronchodilator Forced Expiratory Volume (FEV1) of >/=30% and </=65% of predicted and a post-bronchodilator FEV1 / Forced Vital Capacity (FVC) of </=70% Current or ex-smokers with a smoking history of more than 10 pack-years Patients must be able to produce acceptable induced sputum samples (as defined in the Study Procedure Manual) Normal body weight: Body Mass Index (BMI) between 19 and 35 kg/m2 Exclusion Criteria: Significant respiratory disease other than COPD as bronchial asthma, Cystic fibrosis or clinically evident bronchiectasis More than one COPD exacerbation within 12 months and within 8 weeks prior to screening total blood eosinophil count >/=600/mm3 Thoracotomy with pulmonary resection Regularly use of daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits Hypersensitivity to the investigational drug or to other quinolones and/or to inactive constituents of the inhalation powder Hypersensitivity of the bronchial system to inhalation of nebulized drugs or saline solution Patients with a history of severe allergies, non-allergic drug reactions, or multiple drug allergies Concomitant use of medication which could interfere with the investigational drug. Before study drug administration a wash out period of more than 5 half lives has to be considered Concomitant inhalative therapy with antibiotics and/or concomitant systemic therapy with fluoroquinolones Oral beta-andrenergics, beta blockers oral steroids Methylxanthines: 24-hour washout of short-acting theophylline and 48-hour washout of long-acting theophylline prior to pre-study examination Antihistamines, antileukotrienes prescribed for asthma oral cromolyn sodium or oral nedocromil sodium

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Ciprofloxacin (PulmoSphere, BAYQ3939)<br>* 32.5 mg ciprofloxacin betaine corresponding to 50 mg Ciprofloxacin PulmoSphere inhalation powder will be given as an initial single-dose inhalation (day 0).During the multiple-dose phase (day 2 to day 11), the same dose will be given twice daily, with a concluding single dose (on day 12)<br>|
| Experimental: Arm 2<br> | Drug: Ciprofloxacin (PulmoSphere, BAYQ3939)<br>* 48,75 mg ciprofloxacin betaine corresponding to 75 mg Ciprofloxacin PulmoSphere inhalation powder will be given as an initial single-dose inhalation (day 0).During the multiple-dose phase (day 2 to day 11), the same dose will be given twice daily, with a concluding single dose (on day 12)<br>|
| Placebo Comparator: Arm 3<br> | Drug: Placebo<br>* Placebo inhalation powder will be given as an initial single-dose inhalation (day 0).During the multiple-dose phase (day 2 to day 11), placebo will be given twice daily, with a concluding single dose (on day 12)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital signs |  | Within 28 days after first treatment | 
| Electrocardiogram (ECG) |  | Within 28 days after first treatment | 
| Pulmonary function test |  | Within 28 days after first treatment | 
| Pulse-oximetry |  | Within 12 days after first treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ciprofloxacin concentrations in blood |  | Within 14 days after first treatment | 
| Ciprofloxacin concentrations in urine |  | Within 14 days after first treatment | 
| Ciprofloxacin concentrations in sputum |  | Within 14 days after first treatment | 
| Ciprofloxacin concentrations in mouth fluid |  | Within 7 days after first treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ciprofloxacin, Inhalation, Pharmacokinetics, Safety, Tolerability, COPD