MP-376 (Aeroquin™, Levofloxacin for Inhalation) in Patients With Cystic Fibrosis

Study Overview
=================
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. Decreased efficacy, intolerance and high treatment burden with currently available therapies indicate a need for additional therapies. MP-376 (Aeroquin™) is a novel formulation of the fluoroquinolone levofloxacin that has been optimized for aerosol delivery. Preclinical and clinical studies conducted to date show that aerosol doses of MP-376 are safe and well tolerated, exert an antimicrobial effect, improve lung function and reduce the need for other anti-pseudomonal antibiotics. High concentrations of levofloxacin in the lung delivered as MP-376 are active against CF pathogens including those with high minimum inhibitory concentration (MIC) levels to aminoglycosides such as tobramycin (TOBI®) and other inhaled antimicrobial agents. Inhaled MP-376 can be delivered rapidly and efficiently using a customized PARI investigational configuration of the eFlow® nebulizer system.

Detailed Description
-----------------
This trial will be a double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin administered as MP-376 given for 28 days by the aerosol route to CF patients.

Official Title
-----------------
A Phase 3, Multi-Center, Multinational, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Efficacy And Safety Of MP-376 (Levofloxacin Inhalation Solution; Aeroquin™) In Stable Cystic Fibrosis Patients

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Drug: MP-376 (Levofloxacin solution for Inhalation)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria (selected): >/= 12 years of age Confirmed Diagnosis of Cystic Fibrosis Positive sputum culture for P. aeruginosa at screening and within the past 12 months Patients are able to elicit an 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 28 days Able to reproducibly produce sputum and perform spirometry Exclusion Criteria (selected): Use of any nebulized or systemic antibiotics within 28 days prior to baseline History of hypersensitivity to fluoroquinolones or intolerance with aerosol medication Evidence of respiratory infections within 14 days prior to dosing CrCl < 20ml/min or < 20ml/min/1.73 m2 at Screening

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Inhaled MP-376 (Aeroquin) | Drug: MP-376 (Levofloxacin solution for Inhalation)<br>* 240 mg of MP-376 administered BID for 28 days<br>|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* same volume and frequency as study drug<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to an exacerbation |  | 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to administration of other anti-pseudomonal antimicrobials |  | 56 days | 
| Evaluate changes in FEV1, FEF 25-75 and FVC from baseline to end of treatment |  | 28 days | 
| Changes in bacterial load and susceptibility patterns of isolated organisms from baseline to end of treatment |  | 28 days | 
| Changes in respiratory domain of CFQ-R from baseline to end of treatment baseline to end of treatment |  | 28 days | 
| Evaluate the safety of MP-376 administered over 28 days, compared to placebo |  | 56 days |