• Males or females aged ≥18 years of age for cohorts 1-4; males or females ≥12 years of age for cohort 5.

• Diagnosis of CF based on the following: historical positive sweat chloride value ≥ 60 mEq/L, and/or genotype with two identifiable mutations consistent with CF, accompanied by one or more clinical features consistent with the CF phenotype.

• History of P. aeruginosa-positive sputum cultures or throat swabs with at least 50% positive in the year preceding screening.

• P. aeruginosa-positive sputum culture at screening.

• Forced expiratory volume in 1 second (FEV1) ≥ 40 and ≤ 90% predicted per Global Lung Function Initiative (GLI) equation, pre- or post-bronchodilator.

• Must be able to withhold all other inhaled tobramycin from Day -28 to Day 28 of study participation. Must be able to withhold all other inhaled antibiotics from Day -14 to Day 28.

• Medically stable with no evidence of significant new or acute respiratory symptoms within 30 days prior to screening.

• Hematology, clinical chemistry, and urinalysis results with no clinically significant abnormalities that would interfere with the study assessments at screening as determined by the investigator.

• Female subjects of childbearing potential, defined as not surgically sterile or at least 2 years postmenopausal, must agree to use one of the following forms of contraception from screening through the Day 28 visit: hormonal (oral, implant, or injection) begun \> 30 days prior to screening, barrier (condom, diaphragm with spermicide), intrauterine device, or vasectomized partner (6 months minimum).

• Male subjects must show documentation of infertility or agree to use condoms during study participation.

• Must be able to communicate with site personnel and to understand and voluntarily sign the Informed Consent Form, and be capable and willing to complete all study visits and perform all study required procedures.