Safety, Tolerability and Efficacy of MP-376 Given for 28 Days to Cystic Fibrosis (CF) Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mpex Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00677365
First received: May 12, 2008
Last updated: May 8, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis (CF)
Drug: MP-376
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Mpex Pharmaceuticals:

Primary Outcome Measures:
  • Change in P. Aeruginosa Density [ Time Frame: from baseline to end of treatment (28 days) ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Time to Administration of Other Anti-pseudomonal Antimicrobials [ Time Frame: from baseline until final study visit (up to 56 days) ] [ Designated as safety issue: No ]
    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

  • Percent Change in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: from baseline to end of the 28-day treatment period (28 days) ] [ Designated as safety issue: Yes ]
    Percent change in the amount of air the patient could exhale in 1 second

  • Change in FEV1 Percent Predicted [ Time Frame: from baseline to the end of the treatment 28-day treatment period (28 days) ] [ Designated as safety issue: Yes ]
    Change in the predicted percent of air the patient could exhale in one second

  • 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) ] [ Designated as safety issue: No ]
    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

  • Changes in Susceptability Patterns of Isolated Organisms [ Time Frame: from baseline until the end of the 28-day treatment period (28 days) ] [ Designated as safety issue: No ]
    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


Enrollment: 151
Study Start Date: June 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo inhaled either once or twice daily via the PARI eFlow nebulizer for 28 days
Drug: Placebo
same frequency as study drug using the same nebulizer
Experimental: MP-376 120 mg QD
MP-376 120 mg inhaled Once Daily (QD) via the PARI eFlow nebulizer for 28 days
Drug: MP-376
3 dose regimens of MP-376 administered twice daily (BID) or once daily (QD) for 28 days
Other Names:
  • Levofloxacin Inhalation Solution
  • Aeroquin
Experimental: MP-376 240 mg QD
MP-376 240 mg inhaled QD bia the PARI eFlow nebulizer for 28 days
Drug: MP-376
3 dose regimens of MP-376 administered twice daily (BID) or once daily (QD) for 28 days
Other Names:
  • Levofloxacin Inhalation Solution
  • Aeroquin
Experimental: MP-376 240 mg BID
MP-376 240 mg inhaled twice daily (BID) via the PARI eFlow nebulizer for 28 days
Drug: MP-376
3 dose regimens of MP-376 administered twice daily (BID) or once daily (QD) for 28 days
Other Names:
  • Levofloxacin Inhalation Solution
  • Aeroquin

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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 limite of normal (ULN) at Screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00677365

  Hide Study Locations
Locations
United States, Alabama
Mobile, Alabama, United States, 36608
United States, Arizona
Phoenix, Arizona, United States, 85016
Tucson, Arizona, United States, 85724
United States, Arkansas
Little Rock, Arkansas, United States, 72202
United States, California
Los Angeles, California, United States, 90033
Childrens Hospital
Los Angeles, California, United States, 90027
Oakland, California, United States, 94611
Orange, California, United States, 92868
Palo Alto, California, United States, 94304
Sacramento, California, United States, 95817
San Diego, California, United States, 92103
United States, Florida
Miami, Florida, United States, 33136
Orlando, Florida, United States, 32801
United States, Illinois
Chicago, Illinois, United States, 60025
Oak Lawn, Illinois, United States, 60453
Park Ridge, Illinois, United States, 60068
United States, Iowa
Iowa City, Iowa, United States, 52242
United States, Kentucky
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Boston, Massachusetts, United States, 02115
United States, Michigan
Ann Arbor, Michigan, United States, 48109
Kalamazoo, Michigan, United States, 49007
United States, Minnesota
Minneapolis, Minnesota, United States
United States, Nevada
Las Vegas, Nevada, United States, 89107
United States, New Jersey
Morristown, New Jersey, United States, 07962
United States, New York
Albany, New York, United States, 12208
Valhalla, New York, United States, 10595
United States, Ohio
Cincinnati, Ohio, United States, 45224
Columbus, Ohio, United States, 43205
Dayton, Ohio, United States, 45404
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73112
Oklahoma CF Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19102
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Charleston, South Carolina, United States, 29425
Columbia, South Carolina, United States, 29203
United States, Tennessee
Memphis, Tennessee, United States, 38105
United States, Texas
San Antonio, Texas, United States, 78212
Tyler, Texas, United States, 75708
United States, Utah
Salt Lake City, Utah, United States, 84132
Germany
Berlin, Germany
Essen, Germany
Frankfurt, Germany
Gerlingen, Germany
Gieben, Germany
Kiel, Germany
Munchen, Germany
Tubingen, Germany
Netherlands
Amsterdam, Netherlands
Groesbeek, Netherlands
Rotterdam, Netherlands
Sponsors and Collaborators
Mpex Pharmaceuticals
Investigators
Principal Investigator: Douglas J Conrad, M.D. UCSD
  More Information

No publications provided by Mpex Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mpex Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00677365     History of Changes
Other Study ID Numbers: Mpex-204
Study First Received: May 12, 2008
Results First Received: September 4, 2011
Last Updated: May 8, 2012
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: Dutch Health Care Inspectorate

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 23, 2014