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

Cystic Fibrosis (CF) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00677365
• Other study ID #: Mpex-204
• Secondary ID: 2008-001728-30
• Status: Completed
• Phase: Phase 2
• First received: May 12, 2008
• Last updated: January 17, 2018
• Start date: June 2008
• Est. completion date: June 2009

Study information

• Verified date: January 2018
• Source: Horizon Pharma USA, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Cystic Fibrosis (CF)
• Fibrosis

Intervention

Drug:
• MP-376
3 dose regimens of MP-376 administered twice daily (BID) or once daily (QD) for 28 days
• Placebo
same frequency as study drug using the same nebulizer

Locations

Country	Name	City	State
United States	Childrens Hospital	Los Angeles	California
United States	Oklahoma CF Center	Oklahoma City	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Horizon Pharma USA, Inc.

Countries where clinical trial is conducted

United States,  Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in P. Aeruginosa Density	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	from baseline to end of treatment (28 days)
Secondary	Time to Administration of Other Anti-pseudomonal Antimicrobials	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	from baseline until final study visit (up to 56 days)
Secondary	Percent Change in Forced Expiratory Volume in 1 Second (FEV1)	Percent change in the amount of air the patient could exhale in 1 second	from baseline to end of the 28-day treatment period (28 days)
Secondary	Change in FEV1 Percent Predicted	Change in the predicted percent of air the patient could exhale in one second	from baseline to the end of the treatment 28-day treatment period (28 days)
Secondary	Changes in Respiratory Domain Scores of Cystic Fibrosis Questionnaire - Revised (CFQ-R)	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	from baseline to the end of the 28-day treatment period (28 days)
Secondary	Changes in Susceptability Patterns of Isolated Organisms	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	from baseline until the end of the 28-day treatment period (28 days)