• Treatment emergent adverse events up to end of treatment [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  
• Treatment emergent marked laboratory abnormalities up to 28 days after study medication discontinuation [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]
  
• Treatment emergent pulmonary function test (PFT) abnormalities post-dose for acute tolerability assessment [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  
• Treatment emergent pulmonary function test (PFT) abnormalities up to end of treatment [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]
  
• Adverse events leading to permanent discontinuation of study medication [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  
• Serious adverse events up to 28 days after study medication discontinuation [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  

• To access pharmacokinetics (PK) of Arikace™ in serum and urine, and evaluate sputum amikacin levels [ Time Frame: 28 days dosing ] [ Designated as safety issue: Yes ]
  
• To evaluate change in Pulmonary function [ Time Frame: 28 days dosing ] [ Designated as safety issue: Yes ]
  
• To evaluate change in density of Pseudomonas aeruginosa in sputum [ Time Frame: 28 days dosing ] [ Designated as safety issue: Yes ]
  
• To evaluate time to and duration of systemic anti-Pseudomonal rescue therapy [ Time Frame: 28 days dosing ] [ Designated as safety issue: Yes ]
  
• To evaluate change in St. George's Respiratory Questionnaire measurements [ Time Frame: 28 days dosing ] [ Designated as safety issue: No ]
  

Bronchiectasis is a chronic disorder of the major bronchi and bronchioles characterized by permanent dilation, microbial infection, a persistent inflammatory response with the release of immune mediators and microbial toxins leading to destruction. The origin of bronchiectasis varies, but the presence of microbial infection and a persistent inflammatory response is typical of the disease. The chronic nature of the infection and the associated considerable morbidity provides the rationale for using aerosolized antibiotics for the treatment of bronchiectasis patients.

This is a multi-national Phase 2 study of safety and tolerability of 28 days of daily dosing with two dose levels (280 mg and 560 mg) of Arikace™ versus placebo in subjects with bronchiectasis (BR) and chronic pseudomonas infection. Study subjects will be randomized to receive either study drug or placebo by inhalation via a PARI eFlow nebulizer. Each subject will complete 28 days of daily dosing. All study subjects will be followed for microbiologic activity for 14 days after completion of treatment and for safety for 28 days post completion of study treatment.

The total study duration will be 56 days, with screening visit occurring within the preceding 14 days prior to study day 1. At Day 1 (baseline), subjects will be evaluated at pre-dose and during the first 4-5 hours post-dose. Subjects will return at 2 weeks (day 14) after start of treatment and at the end of 4 weeks (Day 28) treatment period to determine safety and, efficacy of Arikace™. Subjects will be followed up at study days 42 and 56 (about 2 and 4 weeks after end of treatment) for safety determination. After completion of this study, subjects will be, followed up for an additional 6 months via phone contacts and records review, if hospitalized or treated for pulmonary exacerbation (under the extension protocol).

Clinical laboratory parameters, audiology testing, clinical adverse events and pulmonary function will be evaluated for all study subjects in order to determine the qualitative and quantitative safety and tolerability of Arikace™ compared to placebo. Serum, urine and sputum specimens will be collected at periodic intervals to assess PK in subjectswho consent for the PK portion of the study. Additionally, sputum samples will be collected to determine changes in bacterial density. Total Pulmonary Symptom Severity Score will be assessed, and Respiratory quality of life will be evaluated by using the St. George's Respiratory Questionnaire (SGRQ).