Safety, Tolerability and Pharmacokinetics of MP-376 Administered for 14 Days to Stable Pediatric (CF) Patients

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. MP-376 is a novel formulation of the fluoroquinolone levofloxacin that has been optimized for aerosol delivery using the PARI electronic eFlow® nebulizer. Preclinical and early clinical studies in adults show that aerosol doses of MP-376 appear to be safe and well tolerated, and exert an antimicrobial effect when administered once or twice daily. High concentrations of levofloxacin in the lung delivered using MP-376 are expected to be active against CF pathogens such as P. aeruginosa and S. aureus, including those resistant to aminoglycosides (such as TOBI®) and other inhaled antimicrobial agents. Inhaled MP-376 can be delivered rapidly and efficiently using the PARI eFlow® nebulizer system. This Phase 1 study is being performed to obtain safety, tolerability and PK data in children ages 6-16 in order to determine if MP-376 is safe, prior to enrolling children of these ages in the planned pivotal Phase 3 studies.

Detailed Description
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A Phase 1B, Multi-Center, Open Label Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MP-376 Inhalation Solution given Daily for 14 Days to Stable Pediatric Cystic Fibrosis Patients.

Official Title
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A Phase 1B, Multi-Center, Open Label Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MP-376 Inhalation Solution Given Daily for 14 Days to Stable Pediatric Cystic Fibrosis Patients.

Conditions
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Cystic Fibrosis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (selected): 6 to 16 years of age (inclusive) at Visit 1 Weight is greater than or equal to 14 kilograms (kg) Confirmed Diagnosis of Cystic Fibrosis Patients are able to elicit an FEV1 >/= 25% of predicted value (Wang criteria) Clinically stable with no changes in health status within the last 14 days Able to reproducibly undergo spirometry testing Exclusion Criteria (selected): Use of any nebulized or systemic antibiotics within 7 days prior to baseline History of intolerance or hypersensitivity to fluoroquinolones or intolerance with aerosol medications including bronchodilators CrCl < 50mL/min/1.73m2, AST, ALT or total bilirubin >/= 3 x ULN at Screening or evidence of severe liver disease

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>CF PATIENTS 6-11 YEARS OF AGE | Drug: MP-376 (Levofloxacin solution for Inhalation)<br>* DOSE BASED ON PATIENTS WEIGHT<br>|
| Experimental: 2<br>CF PATIENTS 12-16 YEARS OF AGE | Drug: MP-376 (Levofloxacin solution for Inhalation)<br>* DOSE BASED ON PATIENTS WEIGHT<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 for 14 days to CF patients ages 6-16 |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum PK Profile of MP-376 administered for 14 days to CF patients ages 6-16 |  | 21 days | 
| Sputum PK Profile of MP-376 administered for 14 days to CF patients ages 6-16 |  | 21 days | 
| Evaluate changes in FEV1 and FVC from baseline to end of treatment |  | 21 Days |