Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKAYCE™) - Extension Phase

Inclusion Criteria

• Written informed consent obtained from the patient or designated legal guardian prior to the performance of any study related procedures.
• Male or female study subjects ≥ 6 years of age or older.
• Confirmed diagnosis of CF defined as a positive sweat chloride > 60 milliequivalents (mEq)/liter (by pilocarpine iontophoresis) and/or a genotype with 2 identifiable mutations consistent with CF accompanied by one or more clinical features of the CF phenotype.
• History of chronic infection with P. aeruginosa (defined as 3 documented positive cultures in the prior 2 years of which at least one was obtained in the 3 months prior to randomization). The cultures could be obtained from the following respiratory secretions: sputum, throat swabs, nasopharyngeal swabs, or broncho-alveolar lavage fluid specimens.
• Study subjects must produce a screening specimen (expectorated or induced sputum, throat swabs, nasopharyngeal swabs, or broncho-alveolar lavage fluid) that is positive for growth of P. aeruginosa.
• FEV1 ≥ 40% of predicted at Screening.
• SaO2 ≥ 90% at Screening while breathing room air.
• Ability to comply with study medication use, study visits, and study procedures as judged by the investigator.
• Ability to produce 0.5 grams sputum or be willing to undergo an induction to produce sputum for clinical evaluation.
• Clinically stable with no evidence of acute upper or lower respiratory tract infection or history of pulmonary exacerbation within the 4 weeks prior to Screening.

Main criteria for inclusion of patients participating in the 18-month extension period:

• Written informed consent obtained from the patient or designated legal guardian prior to the performance of any study-related procedures in the extension period.
• Patient meets all of the above listed inclusion criteria (1-10) of the main protocol.

Exclusion Criteria

• Administration of any investigational drug within 8 weeks prior to Screening.
• Emergency room visit or hospitalization for CF or respiratory-related illness within the 4 weeks prior to Screening.
• History of alcohol, medication, or illicit drug abuse within the 1 year prior to Screening.
• History of lung transplantation.
• Female of childbearing potential who is lactating or is not practicing an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD).
• Positive pregnancy test. All women of childbearing potential will be tested.
• Use of any anti-pseudomonal antibiotics (IV antibiotics, all inhalation antibiotics, oral fluoroquinolones) within the 28 days prior to Screening.
• Initiation of chronic therapy (i.e. TOBI®, high-dose ibuprofen, rhDNase, macrolide antibiotics) within the 28 days prior to Screening.
• History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of Screening.
• History of mycobacterial and/or Aspergillus infection requiring treatment within 2 years prior to Screening, and/or history of allergic bronchopulmonary aspergillosis (ABPA).
• History of biliary cirrhosis with portal hypertension, or splenomegaly (refer to study manual).
• GGT, AST, or ALT ≥ 3 times the upper limit of normal at Screening visit.
• ANC ≤ 1000 performed at Screening visit.
• Serum creatinine > 1.5 times normal performed at Screening visit.
• History of daily, continuous oxygen supplementation or requirement for more than 2 L/min at night.
• Change in chest x-ray at Screening (or within the 3 months prior to Screening) with new onset infiltrates or that which compromise the safety of the study patient or the quality of the study data.

Main criteria for exclusion of patients participating in the 18 months extension period:

• Patient meets any criteria for exclusion as listed above in the main protocol.
• Patient who met any criteria for study drug discontinuation in the main protocol (TR02-105).