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

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

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)

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Ciprofloxacin (PulmoSphere, BAYQ3939); Drug: Ciprofloxacin (PulmoSphere, BAYQ3939); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: Ciprofloxacin (PulmoSphere, BAYQ3939); 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); Drug: Ciprofloxacin (PulmoSphere, BAYQ3939); 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)
Experimental: Arm 2	Drug: Ciprofloxacin (PulmoSphere, BAYQ3939); 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); Drug: Ciprofloxacin (PulmoSphere, BAYQ3939); 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)
Placebo Comparator: Arm 3	Drug: Placebo; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: August 17, 2009
• First Submitted That Met QC Criteria: August 17, 2009
• First Posted (Estimate): August 18, 2009

Study Record Updates

• Last Update Posted (Estimate): April 1, 2014
• Last Update Submitted That Met QC Criteria: March 31, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Safety; COPD; Pharmacokinetics; Tolerability; Inhalation; Ciprofloxacin
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; 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: 13014; 2008-006771-79 (EudraCT Number)