Study to Characterize Lung Deposition, Pharmacokinetics, Safety and Tolerability of Single Inhalations of Radiolabeled Ciprofloxacin Dry Powder in Healthy Subjects and Patients With Chronic Lung Diseases

NCT01538667 | Completed Phase 1

• 2 other identifiers: 115232011-000342-38
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to characterize variability and extent of the deposition of ciprofloxacin in the respiratory tract of healthy subjects in comparison to patients with chronic lung diseases after inhalation of a single 50 mg dry powder dose containing 32 mg active substance. In addition the safety and pharmacokinetics of ciprofloxacin will be evaluated. In this study the radiolabeled substance will be administered and scintigraphy imaging techniques will be used to demonstrate the lung deposition visually. In the healthy subjects an additional pharmacokinetic method is used to calculate lung deposition indirectly based on pharmacokinetic data derived from plasma. For this purpose they will inhale at a separate occasion another dose of ciprofloxacin after having ingested activated charcoal. The latter serves to bind ciprofloxacin which is swallowed down during the inhalation maneuver in the gastrointestinal (GI) tract, thus preventing its uptake into the blood (charcoal block). Safety investigations will focus on local tolerability in the lung. Pharmacokinetics is to see how the body absorbs, distributes, breaks down and gets rid of the study drug. Results from this study will be used to show how the drug is distributed in the human lung.

Conditions

Respiratory System

Keywords

Lung; Scintigraphy; Pharmacokinetics; Inhalation; Ciprofloxacin

Outcome Measures

Primary Outcomes (1)

• Ciprofloxacin pharmacokinetics including lung deposition

  Firstly, scintigraphic imaging, a non-invasive method using a radioactive (99mTc-) label tagged to the formulation, will be used to describe the distribution and deposition of a single inhaled dose of Ciprofloxacin Dry Powder Inhalation (DPI) in the lung quantitatively. Secondly, based on blood sampling over a period of 24 hours after inhalation non-compartmental pharmacokinetic parameters of ciprofloxacin will be calculated to determine the systemic exposure to drug following inhalation of a single 32.5 mg Ciprofloxacin dose.

  Within 24 hours after treatment

Secondary Outcomes (1)

• Adverse Events collection

  Within 30 days

Study Arms (4)

Arm 1

EXPERIMENTAL

Drug: Ciprofloxacin (Cipro Inhale, BAYQ3939)

Arm 2

EXPERIMENTAL

Drug: Ciprofloxacin (Cipro Inhale, BAYQ3939)

Arm 3

EXPERIMENTAL

Drug: Ciprofloxacin (Cipro Inhale, BAYQ3939)

Arm 4

EXPERIMENTAL

Drug: Ciprofloxacin (Cipro Inhale, BAYQ3939)

Interventions

Ciprofloxacin (Cipro Inhale, BAYQ3939) DRUG

50 mg single powder dose of 99mTc labeled ciprofloxacin PulmoSphere inhalation powder inhaled by healthy subjects

Arm 1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understanding of the study and written informed consent prior to any study-related procedures
• Age: 18 to 65 years (inclusive) at screening visit
• Males
• Non- or ex-smokers who smoked \< 5 pack-years and stopped smoking \> 1 year prior to screening visit
• Results of laboratory tests within the normal ranges; minor deviations are acceptable provided that they are not judged clinically significant by the investigator
• Age: 40 to 70 years (inclusive) at screening visit
• Males and females
• All patients must have a diagnosis of COPD of Stage II or III according to the GOLD (Global Initiative for Chronic Obstructive Lung Disease) Classification (post-bronchodilator forced expiratory volume in 1 second (FEV1): 80% \> FEV1 ≥ 30% of predicted values and a post-bronchodilator FEV1/FVC ≤ 70% (FVC = forced vital capacity)
• Minimum smoking history of 10 pack-years
• Age: 18 to 75 years (inclusive) at screening visit
• Males and females
• Diagnosis of bronchiectasis

You may not qualify if:

• Known hypersensitivity, allergy or intolerance to study drug formulation ingredients
• Febrile illness within 1 week prior to screening visit
• Concomitant severe diseases (judged by the investigator) or diseases which are contraindications for the use of inhaled ciprofloxacin
• Use of ciprofloxacin within 30 days before screening visit
• Use of systemic or topical medicines or substances which oppose the study objectives or which might influence them, e.g. systemic administration of antibiotics which are subject to renal excretion (e.g. beta-lactam antibiotics, levofloxacin, ofloxacin, etc.), furosemide and antacids
• Donation of more than 450 mL of blood within 4 weeks before screening visit
• Clinically relevant findings in the ECG
• Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical investigation
• Participation in another clinical study less than 8 weeks prior to screening visit
• Pulmonary exacerbation within the 6 weeks prior to screening
• History of lung transplant or any lung surgery or on any thoracic surgery waiting list
• Lung function measurements outside normal limits (Normal values: FEV1/FVC \> 70% and FEV1 and FVC \> 80% of predicted)
• Regular use of daytime oxygen therapy
• Diagnosis of bronchial asthma
• Diagnosis of clinically evident bronchiectasis (COPD patients)

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

Unknown Facility

Gauting, Bavaria, 82131, Germany

Location

MeSH Terms

Conditions

Respiratory Aspiration

Interventions

Ciprofloxacin

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2012
• First Posted: February 24, 2012
• Study Start: April 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: August 21, 2014

Record last verified: 2014-08

Locations

DE (1)