A Phase 1b Study to Evaluate the Safety and PK of MP-376 in Chronic Obstructive Pulmonary Disease (COPD) Patients

Patients with Chronic Obstructive Pulmonary Disease (COPD) suffer from frequent and recurrent acute exacerbations (AECB) which are associated with enormous healthcare expenditures and significant morbidity, specifically an increased risk of death, a decline in pulmonary function and a significant change in quality of life. Bacteria appear to have an important role in acute exacerbations in chronic bronchitis and COPD. Studies of acute exacerbations in COPD have shown a reduction in bacterial load with prolonged exacerbation-free interval. In addition, recent studies indicate that acquisition of a new strain of H. influenzae, M. catarrhalis, S. pneumoniae or P. aeruginosa are responsible for many of these exacerbations. Chronic inflammation and bacterial infection predispose many patients to frequent and recurrent acute exacerbations.

Mpex believes that intermittent administration of inhaled MP-376 in high risk patients will decrease the incidence of acute exacerbations by both by lowering the organism burden, and resultant inflammation, as well as pre-emptive eradication of any newly acquired bacterial strains.

This study will be a Phase 1b, multi-center, randomized, single-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of MP-376 solution for inhalation given for 5 days to COPD patients.

• Drug: MP-376 (Levofloxacin solution for Inhalation)
  Daily for 5 days
• Drug: Placebo
  same frequency as MP-376

• Experimental: 1
  MP-376 Inhalation Solution
  Intervention: Drug: MP-376 (Levofloxacin solution for Inhalation)
• Placebo Comparator: 2
  Placebo
  Intervention: Drug: Placebo

Inclusion Criteria (selected):

• >/= 40 years of age
• History of COPD
• FEV1 </= 65% of predicted and FEV1/FVC </= 0.7 value at Screening
• Clinically stable with no changes in health status within the last 30 days
• Lifetime smoking history of at least 15 pack-years
• Willing and able to give informed consent

Exclusion Criteria (selected):

• Use of any systemic or inhaled antibiotics within 30 days prior to baseline
• History of hypersensitivity to fluoroquinolones or intolerance with aerosol medication
• CrCl < 50/ml/min, AST, ALT or total bilirubin >/= 3 x ULN at Screening
• Significant or unstable medical conditions