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

• Safety [ Time Frame: 168 and 336 days ]

  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.

• Efficacy [ Time Frame: 28 Days ]
  Percent change in percent predicted FEV1 from Baseline to Day 28

• Safety [ Time Frame: 168 days ]
  Assessment of adverse events and safety from Baseline through Final Visit
• Efficacy [ Time Frame: 28 Days ]
  Percent change in percent predicted FEV1 from Baseline to Day 28

• Changes in respiratory and other domains of CFQ-R from Baseline to Day 28 [ Time Frame: 28 days ]
• Evaluate changes in FEV1 and FVC from Baseline to Day 28 [ Time Frame: 28 days ]
• Changes in bacterial load and susceptability patterns of isolated organisms from Baseline to Day 28 [ Time Frame: 28 days ]

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™).

• Drug: MP-376 (Levofloxacin Solution for Inhalation)
  MP-376 (Aeroquin, Levofloxacin solution for Inhalation) 240 mg administered BID for 28-days treatment followed by 28 days off treatment
  Other Name: (Aeroquin, Levofloxacin solution for Inhalation)
• Drug: TIS (Tobramycin Inhalation Solution)
  Tobramycin Inhalation Solution administered BID over 3 consecutive cycles of 28-days treatment followed by 28 days off treatment
  Other Name: TOBI

• Experimental: Aeroquin
  Aeroquin, Inhaled Levofloxacin (MP-376)
  Intervention: Drug: MP-376 (Levofloxacin Solution for Inhalation)
• Active Comparator: TIS
  Tobramycin Inhalation solution (TIS) [TOBI® Novartis Pharmaceuticals]
  Intervention: Drug: TIS (Tobramycin Inhalation Solution)

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.