Safety, Pharmacokinetic and Pharmacodynamic Study of MP-376 in Patients With Cystic Fibrosis

Study Overview
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Brief Summary
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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 and reduce the emergence of resistant bacteria.

Detailed Description
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This trial will be a single-blind, placebo-controlled, dose escalating between cohorts, single and multi-dose, multi-center study to evaluate the safety, tolerability and pharmacokinetic profile of levofloxacin administered as MP-376 once, then twice daily for 14 days by the aerosol route to CF patients.

Official Title
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Phase I, Single and Multi-dose, Placebo Controlled, Randomized, Dose-Escalation Study to Evaluate the Safety, Tolerability and PK Profile of MP-376 Using the PARI eFlow Nebulizer for 14 Days to CF Patients

Conditions
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Cystic Fibrosis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 16 years of age Confirmed Diagnosis of Cystic Fibrosis Positive sputum culture for P. aeruginosa within the past 6 months Patients are able to elicit an FEV1 >/= 40% of predicted value at screening Clinically stable with no evidence of acute respiratory or lower respiratory infections within 28 days prior to dosing Able to reproducibly perform spirometry measurements and be able to repeatedly produce sputum over several hours Exclusion Criteria: Use of any nebulized or systemic antibiotics within 4 weeks of starting study History of hypersensitivity to fluoroquinolones or intolerance with aerosol medication Uncontrolled diabetes or abnormal renal function Tobacco use (smoking) in the last 30 days

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Inhaled Levofloxacin | Drug: MP-376 (Levofloxacin solution for Inhalation)<br>* 40, 80, 120mg RDD<br>|
| Placebo Comparator: 2<br>Placebo | Drug: placebo<br>* BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of MP-376 administered twice a day for 14 days |  | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate changes in the microbiology of CF sputum after 14 days of treatment with MP-376 |  | 14 days | 
| PK Profile of single-dose vs multi-dose of MP-376 |  | 14 days | 
| Evaluate changes in FEV1 and FVC over 14 days of Treatment |  | 14 days |