Study to Evaluate the Safety and Efficacy of Ciprofloxacin (Inhaled) in Patients With Cystic Fibrosis
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT00645788 |
Recruitment Status
:
Completed
First Posted
: March 28, 2008
Results First Posted
: July 3, 2012
Last Update Posted
: June 9, 2014
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Cystic Fibrosis | Drug: Ciprofloxacin (Cipro Inhale, BAYQ3939) Drug: Placebo | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 288 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of Inhaled Ciprofloxacin Compared to Placebo in Subjects With Cystic Fibrosis |
Study Start Date : | May 2008 |
Actual Primary Completion Date : | January 2011 |
Actual Study Completion Date : | January 2011 |

Arm | Intervention/treatment |
---|---|
Experimental: 32.50 mg Ciprofloxacin DPI (BAYQ3939)
32.50 mg ciprofloxacin DPI (Dry Powder for Inhalation) corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Drug: Ciprofloxacin (Cipro Inhale, BAYQ3939)
32.5 mg ciprofloxacin DPI corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation powder twice a day for 28 days
|
Experimental: 48.75 mg Ciprofloxacin DPI (BAYQ3939)
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation Powder twice a day for 28 days
|
Drug: Ciprofloxacin (Cipro Inhale, BAYQ3939)
48.75 mg ciprofloxacin DPI corresponding to 75 mg Ciprofloxacin PulmoSphere Inhalation powder twice a day for 28 days (Arm 3 and Arm 4 was introduced after amendment 2)
|
Placebo Comparator: Matching Placebo for 32.50 mg
Inhalation of placebo powder formulation matching 32.50 mg ciprofloxacin DPI twice a day for 28 days
|
Drug: Placebo
50 mg matching placebo powder formulation twice a day for 28 days
|
Placebo Comparator: Matching Placebo for 48.75 mg
Inhalation of placebo powder formulation matching 48.75 mg ciprofloxacin DPI twice a day for 28 days
|
Drug: Placebo
75 mg matching placebo powder formulation twice a day for 28 days (Arm 3 and Arm 4 was introduced after amendment 2)
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- Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28‑30 [ Time Frame: Baseline and End of treatment (Day 28-30) ]FEV1: The maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters at body temperature and ambient pressure saturated with water vapor (BTPS). This was recorded at the site using a spirometer. The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
- Change From Baseline in FEV1 at Visits 4, 5, and Follow-up Visits 8 and 9 [ Time Frame: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60). ]FEV1: The maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters at body temperature and ambient pressure saturated with water vapor (BTPS). This was recorded at the site using a spirometer. The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
- Change From Baseline in P. Aeruginosa Density in the Sputum at Visits 4, 5, 7, 8 and 9 [ Time Frame: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 7 (Day 28-30), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60). ]Density of P. aeruginosa in the sputum is expressed as log10 of colony forming units (CFU)/gram (g). The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
- Time to First Pulmonary Exacerbation Requiring Intervention [ Time Frame: Up to visit 9 (Day 56-60) ]Pulmonary exacerbations: Assessment of pulmonary exacerbation was conducted by the treating physician as part of the physical examination. Pulmonary exacerbation was defined by chest examination findings and any or all of the following symptoms: decreased exercise tolerance, increased cough, increased sputum/cough congestion, school or work absenteeism, increased adventitial sounds on the lung examination, and decreased appetite.
- Change From Baseline in Forced Vital Capacity (FVC) at Visits 4, 5, 7, 8 and 9 [ Time Frame: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 7 (Day 28-30), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60). ]FVC: The maximal volume of air exhaled with maximally forced effort from a maximal inspiration, ie, vital capacity performed with a maximally forced expiratory effort expressed in liters at BTPS (body temperature and ambient pressure saturated with water vapor). The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
- Change From Baseline in Forced Expiratory Flow (FEF 25-75%) at Visits 4, 5, 7, 8 and 9 [ Time Frame: Baseline and Visit 4 (Day 7-9), Visit 5 (Day 14-16), Visit 7 (Day 28-30), Visit 8 (Day 41-45), and Visit 9 (Day 56 -60). ]FEF 25-75% (also known as the maximum midexpiratory flow [MMEF]): The mean forced expiration flow over the middle half of the forced vital capacity (FVC). It was taken from the blow with the largest sum of FEV1 and FVC. The later time point minus baseline, days as planned and the last observation carried forward (LOCF) used.
- Number of Participants Developing Ciprofloxacin-resistant Mucoid P.Aeruginosa Isolates [ Time Frame: Baseline and up to visit 9 (day 56-60) ]Susceptibility and resistance assessment of a bacterial isolate was performed using the established Food and Drug Administration (FDA) susceptibility criteria for ciprofloxacin. The susceptibility criteria in mg/L are ≤1 for organisms Enterobacteriaciae, P. aeruginosa, Staphylococcus species and S. pneumoniae. The "susceptible" bacterial species likely responds to typical doses of ciprofloxacin. The resistance criteria for ciprofloxacin in mg/L are ≥4 mg/L for the same organisms. Resistance indicates that the bacteria is less likely to respond to typical doses of ciprofloxacin therapy.
- Number of Participants Developing Ciprofloxacin-resistant Non-mucoid P.Aeruginosa Isolates [ Time Frame: Baseline and up to visit 9 (day 56-60) ]Susceptibility and resistance assessment of a bacterial isolate was performed using the established Food and Drug Administration (FDA) susceptibility criteria for ciprofloxacin. The susceptibility criteria in mg/L are ≤1 for organisms Enterobacteriaciae, P. aeruginosa, Staphylococcus species and S. pneumoniae. The "susceptible" bacterial species likely responds to typical doses of ciprofloxacin. The resistance criteria for ciprofloxacin in mg/L are ≥4 mg/L for the same organisms. Resistance indicates that the bacteria is less likely to respond to typical doses of ciprofloxacin therapy.
- Effect of Ciprofloxacin DPI Treatment on Quality of Life Measured by Cystic Fibrosis Quality of Life Questionnaire Revised (CFQ-R), Respiratory Scale [ Time Frame: Baseline and Visit 7 (Day 28-30) and Visit 9 (Day 56 -60) ]The CF quality of life questionnaire revised (CFQ-R), a validated disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents and adults with cystic fibrosis (CF). It is self-administered and consists of 44 items, divided into 12 generic and disease-specific scales. The scale includes physical functioning, role, vitality, emotional functioning, social functioning, body image, eating disturbances, treatment burden, health perceptions, weight, respiratory symptoms, and digestive symptoms. Scale range: 0 to 100 (maximum). Better outcome with higher values.
- Plasma Concentrations of Ciprofloxacin From Selected Participants During Treatment [ Time Frame: Up to visit 7 (Day 28-30) ]Plasma concentrations measured using validated high pressure liquid chromatography-mass specroscopy/mass spectroscopy (HPLC-MS/MS) methods in selected patients at predefined time windows to contribute pharmacokinetic (PK) information for an inter-study population PK evaluation. Sampling window for Plasma: Predose (trough level), <15 min, 2.0 - 2.5 hour, and 4.0 - 7.0 hours after the end of inhalation. Number of samples vary at different time points.
- Sputum Concentrations of Ciprofloxacin From Selected Participants During Treatment [ Time Frame: Up to visit 7 (Day 28-30) ]Sputum concentrations measured using validated HPLC-MS/MS methods in selected patients to contribute kinetic information for an inter-study population sputum kinetic evaluation. Number of samples vary at different time points.
- Number of Participants With the Occurrence of Drug Induced Bronchospasms [ Time Frame: Up to visit 9 (Day 56-60) ]Bronchospasm reported as adverse event: Bronchospasm defined as >=15% drop in FEV1, and may also include allergic and excercise-induced bronchospasm. Drug-induced bronchospasm: Treatment-emergent bronchospasm was defined as >=15% drop in FEV1 in the ITT/safety population. Note: One of the bronchospasm events was considered a serious adverse event, and it was not included under "other" adverse events. A sum of bronchospasm events was 1+6=7.

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Ages Eligible for Study: | 12 Years and older (Child, Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Subjects, or their legal representative(s), must have given their written informed consent to participate in the study after receiving adequate previous information and prior to any study specific procedures
- Children (12 - 17 years) or adults >/=18 years
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Documented diagnosis Cystic Fibrosis (CF):
- documented sweat chloride >/=60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) or nasal potential difference
- either homozygous for ΔF508 genetic mutation or a compound heterozygous for 2 known CF mutations
- and clinical findings consistent with CF
- Chronic colonization with P. aeruginosa defined as a positive respiratory tract culture (sputum or throat swab) within 12 months prior to screening and at screening (Note: subjects with negative culture at screening can, at the discretion of the investigator, be rescreened at a later date)
- Ability to perform reproducible pulmonary function tests
- Ability to produce sputum (noninduced)
- Stable pulmonary status, FEV1 >/=35% to </=75% (intraindividual variability +/-10% of absolute value). Note: The subject is not eligible for enrollment if the variability results in (or leads to) an FEV1 <35%.
- Room air oximetry >/=88% saturation
- Off antibiotics (except macrolide) and Cipro (oral) for at least 30 days prior to the administration of study drug for pulmonary exacerbation
- Stable regimen of standard CF treatment including chest physiotherapies and exercise regimens should not change during the 30 days prior to the administration of study drug and during the study (including macrolide administration unchanged in the previous 30 days)
- Subjects who are able to understand and follow instructions and who are able to participate in the study for the entire period
- Women who are willing to use an adequate method of contraception for 3 months after receiving the study drug. Adequate methods of contraception include vasectomy or condom use by their partners, diaphragm with spermicidal gel, coil (intrauterine device), surgical sterilization or oral contraceptive
Exclusion Criteria:
- Findings on screening history and physical examination unrelated to CF that could potentially affect the efficacy measurements (eg, chest surgery)
- Subjects with colonization of Pseudomonas aeruginosa and a CIPRO MIC of >/=256 µg/ml or mg/l
- Burkholderia cepacia complex colonization of their respiratory tract within the past 12 months (documented by screen laboratory)
- Known aspergillosis (unless asymptomatic). Patients with invasive disease, ABPA with IGE > 500 mg/dL will be excluded
- Transaminase level >3x upper limit of normal (ULN)
- Massive hemoptysis (>/=300 cc or requiring blood transfusion) in the preceding 4 weeks
- Intravenous antibiotic treatment for pulmonary exacerbation in the past 30 days
- Subjects with a medical disorder, condition or history of such that would impair the subject's ability to participate or complete this study in the opinion of the investigator or the sponsor
- Febrile illness within 1 week before the start of the study
- Active treatment for nontuberculosis mycobacteria
- Exposure to any investigational drug within 30 days
- Any history of allergic reaction to fluoroquinolones or other quinolones
- On oral steroids >20 mg/day for longer than 14 days in the past 3 months
- Creatinine >/=2x ULN

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00645788

United States, Arizona | |
Phoenix, Arizona, United States, 85016 | |
Tucson, Arizona, United States, 85724 | |
United States, Arkansas | |
Little Rock, Arkansas, United States, 72205 | |
United States, California | |
Los Angeles, California, United States, 90027 | |
Los Angeles, California, United States, 90033 | |
Los Angeles, California, United States, 90048 | |
Orange, California, United States, 92868 | |
San Diego, California, United States, 92123-4282 | |
San Francisco, California, United States, 94143 | |
Ventura, California, United States, 93003 | |
United States, Colorado | |
Aurora, Colorado, United States, 80045 | |
United States, Connecticut | |
Hartford, Connecticut, United States, 06102 | |
New Haven, Connecticut, United States, 06520 | |
United States, Florida | |
Jacksonville, Florida, United States, 32207 | |
Miami, Florida, United States, 33136 | |
Orlando, Florida, United States, 32801 | |
Orlando, Florida, United States, 32803 | |
Orlando, Florida, United States, 32806 | |
United States, Georgia | |
Augusta, Georgia, United States, 30912-4005 | |
United States, Illinois | |
Chicago, Illinois, United States, 60612 | |
Chicago, Illinois, United States, 60614 | |
Glenview, Illinois, United States, 60025 | |
Maywood, Illinois, United States, 60153 | |
United States, Indiana | |
Indianapolis, Indiana, United States, 46202 | |
United States, Iowa | |
Iowa city, Iowa, United States, 52242-1089 | |
United States, Kentucky | |
Lexington, Kentucky, United States, 40536-0284 | |
Louisville, Kentucky, United States, 40207 | |
United States, Massachusetts | |
Boston, Massachusetts, United States, 02111 | |
Boston, Massachusetts, United States, 02115 | |
United States, Michigan | |
Ann Arbor, Michigan, United States, 48109 | |
Kalamazoo, Michigan, United States, 49007 | |
United States, Mississippi | |
Jackson, Mississippi, United States, 39216 | |
United States, Nevada | |
Las Vegas, Nevada, United States, 89107 | |
United States, New Jersey | |
Livingston, New Jersey, United States, 07039 | |
Long Branch, New Jersey, United States, 07740 | |
Morristown, New Jersey, United States, 07962 | |
Somerville, New Jersey, United States, 08876 | |
United States, New York | |
Albany, New York, United States, 12208 | |
New Hyde Park, New York, United States, 11040 | |
Valhalla, New York, United States, 10595 | |
United States, North Carolina | |
Durham, North Carolina, United States, 27710 | |
United States, Ohio | |
Akron, Ohio, United States, 44308-1062 | |
Cincinnati, Ohio, United States, 45229-3039 | |
Toledo, Ohio, United States, 43606 | |
United States, Oklahoma | |
Oklahoma City, Oklahoma, United States, 73104 | |
Oklahoma City, Oklahoma, United States, 73112 | |
Tulsa, Oklahoma, United States, 74145 | |
United States, Pennsylvania | |
Hershey, Pennsylvania, United States, 17033-0850 | |
Philadelphia, Pennsylvania, United States, 19104-4283 | |
Philadelphia, Pennsylvania, United States, 19134 | |
United States, South Carolina | |
Charleston, South Carolina, United States, 29425 | |
United States, Tennessee | |
Knoxville, Tennessee, United States, 37916 | |
United States, Texas | |
Austin, Texas, United States, 78723 | |
San Antonio, Texas, United States, 78212 | |
United States, Utah | |
Salt Lake City, Utah, United States, 84132 | |
United States, Virginia | |
Charlottesville, Virginia, United States, 22908 | |
United States, Washington | |
Seattle, Washington, United States, 98105 | |
United States, Wisconsin | |
Madison, Wisconsin, United States, 53792 | |
Australia, Queensland | |
Brisbane, Queensland, Australia, 4029 | |
Chermside, Queensland, Australia, 4032 | |
South Brisbane, Queensland, Australia, 4101 | |
Australia, South Australia | |
Adelaide, South Australia, Australia, 5000 | |
Australia, Victoria | |
Clayton, Victoria, Australia, 3168 | |
Parkville, Victoria, Australia, 3052 | |
Australia, Western Australia | |
Nedlands, Western Australia, Australia, 6009 | |
Canada, Newfoundland and Labrador | |
St. John's, Newfoundland and Labrador, Canada, A1B 3V6 | |
Canada, Ontario | |
Hamilton, Ontario, Canada, L8S 4J9 | |
London, Ontario, Canada, N6A 5B8 | |
Canada, Quebec | |
Montreal, Quebec, Canada, H2X 2P4 | |
Denmark | |
Copenhagen, Denmark, 2100 | |
Germany | |
München, Bayern, Germany, 80336 | |
Frankfurt, Hessen, Germany, 60590 | |
Leipzig, Sachsen, Germany, 04103 | |
Berlin, Germany, 12200 | |
Israel | |
Haifa, Israel | |
Jerusalem, Israel | |
Petach Tikva, Israel | |
Tel Hashomer, Israel | |
Norway | |
Oslo, Norway, 0407 | |
Sweden | |
Göteborg, Sweden, 416 85 | |
Lund, Sweden, 221 85 | |
Uppsala, Sweden, 751 85 | |
United Kingdom | |
Cambridge, Cambridgeshire, United Kingdom, CB3 8RE | |
Southampton, Hampshire, United Kingdom, SO16 6YD | |
Belfast, North Ireland, United Kingdom, BT12 7AB | |
Birmingham, West Midlands, United Kingdom, B9 5SS |
Study Director: | Bayer Study Director | Bayer |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Bayer |
ClinicalTrials.gov Identifier: | NCT00645788 History of Changes |
Other Study ID Numbers: |
12429 2008-008314-40 ( EudraCT Number ) |
First Posted: | March 28, 2008 Key Record Dates |
Results First Posted: | July 3, 2012 |
Last Update Posted: | June 9, 2014 |
Last Verified: | May 2014 |
Keywords provided by Bayer:
Ciprofloxacin cystic fibrosis sweat test pulmonary function test |
Additional relevant MeSH terms:
Fibrosis Cystic Fibrosis Pathologic Processes Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Ciprofloxacin |
Anti-Bacterial Agents Anti-Infective Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Cytochrome P-450 CYP1A2 Inhibitors Cytochrome P-450 Enzyme Inhibitors |