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

Phase 2

Completed

Conditions: Cystic Fibrosis (CF)

Interventions: Drug: MP-376
Drug: Placebo

Registration Number: NCT00677365

Lead Sponsor: Amgen

Brief 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.

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 with completed results acquired from Horizon in 2024.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 151

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MP-376 120 mg QD	MP-376	MP-376 120 mg inhaled Once Daily (QD) via the PARI eFlow nebulizer for 28 days
MP-376 240 mg BID	MP-376	MP-376 240 mg inhaled twice daily (BID) via the PARI eFlow nebulizer for 28 days
Placebo	Placebo	Placebo inhaled either once or twice daily via the PARI eFlow nebulizer for 28 days
MP-376 240 mg QD	MP-376	MP-376 240 mg inhaled QD bia the PARI eFlow nebulizer for 28 days

Primary Outcome Measures

Name	Time	Method
Change in P. Aeruginosa Density	from baseline to end of treatment (28 days)	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

Name	Time	Method
Percent Change in Forced Expiratory Volume in 1 Second (FEV1)	from baseline to end of the 28-day treatment period (28 days)	Percent change in the amount of air the patient could exhale in 1 second
Time to Administration of Other Anti-pseudomonal Antimicrobials	from baseline until final study visit (up to 56 days)	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
Change in FEV1 Percent Predicted	from baseline to the end of the treatment 28-day treatment period (28 days)	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)	from baseline to the end of the 28-day treatment period (28 days)	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	from baseline until the end of the 28-day treatment period (28 days)	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