- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00677365
Safety, Tolerability and Efficacy of MP-376 Given for 28 Days to Cystic Fibrosis (CF) Patients
January 17, 2018 updated by: Horizon Pharma USA, Inc.
Phase II, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety, Tolerability and Efficacy of Three Dosage Regimens of MP-376 Solution for Inhalation Given for 28 Days to Stable CF Patients
Patients with cystic fibrosis (CF) suffer from chronic infections of the lower respiratory tract that can be caused by one or multiple bacteria, including Pseudomonas aeruginosa, which has been particularly problematic to eradicate and been implicated as the major cause of morbidity and mortality in CF patients.
Aerosol delivery of antibiotics directly to the lung increases the local concentrations of antibiotic at the site of infection resulting in improved antimicrobial effects compared to systemic administration.
Bacterial resistance to current aerosol antibiotic treatments indicate a need for improved therapies to treat CF patients with pulmonary infections caused by multi-drug resistant Pseudomonas aeruginosa and other bacteria.
High concentrations of MP-376 delivered directly to the lung are projected to have antimicrobial effects on even the most resistant organisms.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This trial will be a double-blind, placebo-controlled study to evaluate the safety, tolerability and efficacy of levofloxacin administered as MP-376 of three dosage regimens given for 28 days by the aerosol route to CF patients.
Study Type
Interventional
Enrollment (Actual)
151
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Berlin, Germany
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Essen, Germany
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Frankfurt, Germany
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Gerlingen, Germany
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Gieben, Germany
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Kiel, Germany
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Munchen, Germany
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Tubingen, Germany
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Amsterdam, Netherlands
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Groesbeek, Netherlands
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Rotterdam, Netherlands
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Alabama
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Mobile, Alabama, United States, 36608
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Arizona
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Phoenix, Arizona, United States, 85016
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Tucson, Arizona, United States, 85724
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Arkansas
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Little Rock, Arkansas, United States, 72202
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California
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Los Angeles, California, United States, 90033
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Los Angeles, California, United States, 90027
- Childrens Hospital
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Oakland, California, United States, 94611
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Orange, California, United States, 92868
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Palo Alto, California, United States, 94304
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Sacramento, California, United States, 95817
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San Diego, California, United States, 92103
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Florida
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Miami, Florida, United States, 33136
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Orlando, Florida, United States, 32801
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Illinois
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Chicago, Illinois, United States, 60025
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Oak Lawn, Illinois, United States, 60453
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Park Ridge, Illinois, United States, 60068
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Iowa
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Iowa City, Iowa, United States, 52242
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Kentucky
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Louisville, Kentucky, United States, 40202
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Massachusetts
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Boston, Massachusetts, United States, 02115
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Michigan
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Ann Arbor, Michigan, United States, 48109
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Kalamazoo, Michigan, United States, 49007
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Minnesota
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Minneapolis, Minnesota, United States
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Nevada
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Las Vegas, Nevada, United States, 89107
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New Jersey
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Morristown, New Jersey, United States, 07962
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New York
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Albany, New York, United States, 12208
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Valhalla, New York, United States, 10595
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Ohio
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Cincinnati, Ohio, United States, 45224
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Columbus, Ohio, United States, 43205
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Dayton, Ohio, United States, 45404
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73112
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Oklahoma City, Oklahoma, United States, 73104
- Oklahoma CF Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19102
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Pittsburgh, Pennsylvania, United States, 15213
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South Carolina
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Charleston, South Carolina, United States, 29425
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Columbia, South Carolina, United States, 29203
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Tennessee
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Memphis, Tennessee, United States, 38105
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Texas
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San Antonio, Texas, United States, 78212
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Tyler, Texas, United States, 75708
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Utah
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Salt Lake City, Utah, United States, 84132
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
14 years and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria (selected):
- > 16 years of age
- Confirmed Diagnosis of Cystic Fibrosis
- Positive sputum culture for P. aeruginosa within the past 18 months
- Patients are able to elicit a forced expiratory volume in 1 second (FEV1) >/= 25% but </= 85% of predicted value at screening
- Have received at least 3 courses of inhaled antimicrobials over the preceding 12 months
- Clinically stable with no changes in health status within the last 30 days
- Able to reproducibly produce sputum and perform spirometry
Exclusion Criteria (selected):
- Use of any nebulized or systemic antibiotics within 30 days prior to baseline
- History of hypersensitivity to fluoroquinolones or intolerance with aerosol medication
- Evidence of acute upper within 10 days or lower respiratory infections within 30 days prior to dosing
- Creatine clearance < 50mg/ml, aspartate transaminase (AST), alanine transaminase (ALT) or total bilirubin >/= 3 x upper limit of normal (ULN) at Screening
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
Placebo inhaled either once or twice daily via the PARI eFlow nebulizer for 28 days
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same frequency as study drug using the same nebulizer
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Experimental: MP-376 120 mg QD
MP-376 120 mg inhaled Once Daily (QD) via the PARI eFlow nebulizer for 28 days
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3 dose regimens of MP-376 administered twice daily (BID) or once daily (QD) for 28 days
Other Names:
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Experimental: MP-376 240 mg QD
MP-376 240 mg inhaled QD bia the PARI eFlow nebulizer for 28 days
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3 dose regimens of MP-376 administered twice daily (BID) or once daily (QD) for 28 days
Other Names:
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Experimental: MP-376 240 mg BID
MP-376 240 mg inhaled twice daily (BID) via the PARI eFlow nebulizer for 28 days
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3 dose regimens of MP-376 administered twice daily (BID) or once daily (QD) for 28 days
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in P. Aeruginosa Density
Time Frame: from baseline to end of treatment (28 days)
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Patients were required to cough deeply and then spit sputum into a sterile container.
The bacteria contained in the sputum sample was incubated in a laboratory and the number of P. aeruginosa colony forming units per gram of sputum (CFU/g) was determined.
The difference in CFUs/g were then compared from baseline to the conclusion of the 28 day treatment period
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from baseline to end of treatment (28 days)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Administration of Other Anti-pseudomonal Antimicrobials
Time Frame: from baseline until final study visit (up to 56 days)
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Time to administration of other anti-pseudomonal antimicrobials in patients with at least one of the following: decreased exercise tolerance, increased cough, increased sputum/chest congestion, or decreased appetite; 25th percentile data reported
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from baseline until final study visit (up to 56 days)
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Percent Change in Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: from baseline to end of the 28-day treatment period (28 days)
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Percent change in the amount of air the patient could exhale in 1 second
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from baseline to end of the 28-day treatment period (28 days)
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Change in FEV1 Percent Predicted
Time Frame: from baseline to the end of the treatment 28-day treatment period (28 days)
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Change in the predicted percent of air the patient could exhale in one second
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from baseline to the end of the treatment 28-day treatment period (28 days)
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Changes in Respiratory Domain Scores of Cystic Fibrosis Questionnaire - Revised (CFQ-R)
Time Frame: from baseline to the end of the 28-day treatment period (28 days)
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Change in the score from 0 to 100 that a patient reports for their respiratory symptoms in the CFQ-R.
An increase in score illustrates an improvement in symptoms.
An increase of 4 or more is considered clinically significant
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from baseline to the end of the 28-day treatment period (28 days)
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Changes in Susceptability Patterns of Isolated Organisms
Time Frame: from baseline until the end of the 28-day treatment period (28 days)
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All isolates of P. aeruginosa cultures grown from patient sputum samples were evaluated to see whether the minimum concentration of levofloxacin needed to inhibit growth of the bacteria (i.e., minimum inhibitory concentration; MIC) had increased; 2. The MIC50 and MIC90 values were calculated as the 50th percentile value and the 90th percentile value, respectively.
Note that percentile values between dilution values were rounded up to the nearest dilution value
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from baseline until the end of the 28-day treatment period (28 days)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Douglas J Conrad, M.D., UCSD
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2008
Primary Completion (Actual)
June 1, 2009
Study Completion (Actual)
June 1, 2009
Study Registration Dates
First Submitted
May 12, 2008
First Submitted That Met QC Criteria
May 13, 2008
First Posted (Estimate)
May 14, 2008
Study Record Updates
Last Update Posted (Actual)
January 19, 2018
Last Update Submitted That Met QC Criteria
January 17, 2018
Last Verified
January 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Respiratory Tract Diseases
- Lung Diseases
- Infant, Newborn, Diseases
- Genetic Diseases, Inborn
- Pancreatic Diseases
- Fibrosis
- Cystic Fibrosis
- 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
- Anti-Infective Agents, Urinary
- Renal Agents
- Levofloxacin
Other Study ID Numbers
- Mpex-204
- 2008-001728-30 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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