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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
History of Changes
  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:

U.S. FDA Resources

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

  Show 50 Study Locations
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
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Ofloxacin
 Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents

ClinicalTrials.gov processed this record on May 22, 2013