Trial of Aeroquin Versus Tobramycin Inhalation Solution (TIS) in Cystic Fibrosis (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.

Detailed Description
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This study will assess the comparative safety of MP-376 (Aeroquin) and Tobramycin Inhalation solution (TIS) [TOBI® Novartis Pharmaceuticals] over three consecutive cycles of 28-days treatment followed by 28-days off in stable CF patients with chronic P. aeruginosa lung infection. Efficacy data for MP-376 and TIS at the end of the first 28-day treatment period will also be compared, as well as explored over multiple treatment cycles. Study patients participating in Mpex 209 will be given the option to participate in a six-month open label extension phase of the Mpex 209 protocol. The open label extension will allow enrolled patients to receive three additional courses of MP-376 (levofloxacin inhalation solution, Aeroquin™).

Official Title
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Phase 3, Open-label, Randomized Trial to Evaluate the Safety and Efficacy of MP-376 Inhalation Solution (Aeroquin) vs. Tobramycin Inhalation Solution (TIS) in Stable CF Patients

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: MP-376 (Levofloxacin Solution for Inhalation)
* Drug: TIS (Tobramycin Inhalation Solution)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (selected): > 12 years of age Confirmed Diagnosis of Cystic Fibrosis Positive sputum culture for P. aeruginosa 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 tobramycin 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 inhaled or systemic aminoglycosides including tobramycin or any excipients Evidence of acute upper within 10 days or lower respiratory infections within 28 days prior to dosing CrCl < 20 at Screening History of lung transplantation Extension Portion of the Study: Patients enrolled in Mpex 209 are permitted to participate in the open label extension as long as they complete Visit 7 (Day 168), provide informed consent for participation in the open label extension of in the study and are clinically stable, as assessed by the Investigator.

Ages Eligible for Study
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Minimum Age: 12 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: Aeroquin<br>Aeroquin, Inhaled Levofloxacin (MP-376) | Drug: MP-376 (Levofloxacin Solution for Inhalation)<br>* MP-376 (Aeroquin, Levofloxacin solution for Inhalation) 240 mg administered BID for 28-days treatment followed by 28 days off treatment<br>* Other names: (Aeroquin, Levofloxacin solution for Inhalation);|
| Active Comparator: TIS<br>Tobramycin Inhalation solution (TIS) [TOBI® Novartis Pharmaceuticals] | Drug: TIS (Tobramycin Inhalation Solution)<br>* Tobramycin Inhalation Solution administered BID over 3 consecutive cycles of 28-days treatment followed by 28 days off treatment<br>* Other names: TOBI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Assessment of adverse events and safety from Baseline through Final Visit Extension portion of Study: Descriptive statistics for all patients receiving at least one dose of MP-376 in the extension phase of the study will be summarized for the safety, microbiology, and disease-related endpoints. No formal hypothesis tests are planned. | 168 and 336 days | 
| Efficacy | Percent change in percent predicted FEV1 from Baseline to Day 28 | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in respiratory and other domains of CFQ-R from Baseline to Day 28 |  | 28 days | 
| Evaluate changes in FEV1 and FVC from Baseline to Day 28 |  | 28 days | 
| Changes in bacterial load and susceptability patterns of isolated organisms from Baseline to Day 28 |  | 28 days |