Study to Evaluate the Safety and Pharmacokinetics of Inhaled Ciprofloxacin in Patients With Mild to Moderate 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 Mild to Moderate Chronic Obstructive Pulmonary Disease (GOLD I - II), 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 mild to moderate COPD (stage I-II according to GOLD Criteria).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Mannheim, Baden-Württemberg, Germany, 68167

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients with COPD (Stage I or II according to the GOLD Classification), 35 years of age or older
• Airway obstruction with a post-bronchodilator Forced Expiratory Volume (FEV1) > or equal 50% of predicted normal and a post-bronchodilator FEV1 / Forced Vital Capacity (FVC) < 70%.
• Current or ex-smokers with a smoking history of more than 10 pack-years
• Body mass index (BMI) between 18 and 33 kg/m2
• Written informed consent to participate in the study after receiving adequate previous information and prior to any study specific procedures

Exclusion Criteria:

• Significant disease other than COPD as bronchial asthma, cystic fibrosis or clinically evident bronchiectasis
• Total blood eosinophil count >/=600/mm3.
• Thoracotomy with pulmonary resection
• Regular use of daytime oxygen therapy
• Completion of a pulmonary rehabilitation program in the six weeks prior to the pre-study examination or current participation in a rehabilitation program
• 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
• Acute pulmonary exacerbation
• Patients with a history of severe allergies, non-allergic drug reactions, or multiple drug allergies
• Concomitant inhalative therapy with antibiotics and/or concomitant systemic therapy with fluoroquinolones
• Oral beta-adrenergics, beta blockers
• Long acting anti-cholinergics within 2 weeks prior to pre-study examination
• Inhaled or 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
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1	Drug: Ciprofloxacin (Cipro inhale, BAYQ3939); 32.5 mg ciprofloxacin betaine corresponding to 50 mg Ciprofloxacin Pulmosphere inhalation powder will be given as an initial single dose application on day 00d.During the multiple dose phase (day 02d to 10d) the same dose will be given twice daily (bid) with a concluding single dose on 11d.; Drug: Ciprofloxacin (Cipro inhale, BAYQ3939); 32.5 mg ciprofloxacin betaine corresponding to 50 mg Ciprofloxacin Pulmosphere inhalation powder will be given as an initial single dose application on day 00d.During the multiple dose phase (day 02d to 10d) the same dose will be given three times daily (tid) with a concluding single dose on 11d.; Drug: Ciprofloxacin (Cipro inhale, BAYQ3939); 48.75 mg ciprofloxacin betaine corresponding to 75 mg Ciprofloxacin Pulmosphere inhalation powder will be given as an initial single dose application on day 00d.During the multiple dose phase (day 02d to 10d) the same dose will be given twice daily (bid) with a concluding single dose on 11d.
EXPERIMENTAL: Arm 2	Drug: Ciprofloxacin (Cipro inhale, BAYQ3939); 32.5 mg ciprofloxacin betaine corresponding to 50 mg Ciprofloxacin Pulmosphere inhalation powder will be given as an initial single dose application on day 00d.During the multiple dose phase (day 02d to 10d) the same dose will be given twice daily (bid) with a concluding single dose on 11d.; Drug: Ciprofloxacin (Cipro inhale, BAYQ3939); 32.5 mg ciprofloxacin betaine corresponding to 50 mg Ciprofloxacin Pulmosphere inhalation powder will be given as an initial single dose application on day 00d.During the multiple dose phase (day 02d to 10d) the same dose will be given three times daily (tid) with a concluding single dose on 11d.; Drug: Ciprofloxacin (Cipro inhale, BAYQ3939); 48.75 mg ciprofloxacin betaine corresponding to 75 mg Ciprofloxacin Pulmosphere inhalation powder will be given as an initial single dose application on day 00d.During the multiple dose phase (day 02d to 10d) the same dose will be given twice daily (bid) with a concluding single dose on 11d.
EXPERIMENTAL: Arm 3	Drug: Ciprofloxacin (Cipro inhale, BAYQ3939); 32.5 mg ciprofloxacin betaine corresponding to 50 mg Ciprofloxacin Pulmosphere inhalation powder will be given as an initial single dose application on day 00d.During the multiple dose phase (day 02d to 10d) the same dose will be given twice daily (bid) with a concluding single dose on 11d.; Drug: Ciprofloxacin (Cipro inhale, BAYQ3939); 32.5 mg ciprofloxacin betaine corresponding to 50 mg Ciprofloxacin Pulmosphere inhalation powder will be given as an initial single dose application on day 00d.During the multiple dose phase (day 02d to 10d) the same dose will be given three times daily (tid) with a concluding single dose on 11d.; Drug: Ciprofloxacin (Cipro inhale, BAYQ3939); 48.75 mg ciprofloxacin betaine corresponding to 75 mg Ciprofloxacin Pulmosphere inhalation powder will be given as an initial single dose application on day 00d.During the multiple dose phase (day 02d to 10d) the same dose will be given twice daily (bid) with a concluding single dose on 11d.
PLACEBO_COMPARATOR: Arm 4	Drug: Placebo; Placebo inhalation powder will be given as an initial single dose inhalation on 00d.During the multiple dose phase placebo will be given twice/three-times daily with a concluding single dose on day 11d.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Vital signs: evaluated by heart rate, blood pressure, clinical laboratory	Within 28 days after first treatment
Electrocardiogram: evaluated by shape and time intervals	Within 28 days after first treatment
Pulmonary function test evaluated by FEV1	Within 28 days after first treatment
Pulse oximetry by peripheral oxygen concentration	Within 12 days after first treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Determination of ciprofloxacin concentration in blood	Within 14 days after first treatment
Determination of ciprofloxacin concentration in urine	Within 14 days after first treatment
Determination of ciprofloxacin concentration in sputum	Within 14 days after first treatment
Determination of ciprofloxacin concentration in oral rinsing fluid	Within 7 days after first treatment

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Novartis

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): September 1, 2009
• Study Completion (ACTUAL): September 1, 2009

Study Registration Dates

• First Submitted: October 15, 2009
• First Submitted That Met QC Criteria: January 19, 2010
• First Posted (ESTIMATE): January 20, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): May 30, 2013
• Last Update Submitted That Met QC Criteria: May 29, 2013
• Last Verified: May 1, 2013

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: 13013; 2008-006770-14 (EUDRACT_NUMBER)