This study will determine the safety, tolerability, and pharmacokinetics of a single dose of GS-5737 administered with a 2.8% saline solution vehicle in adult subjects with CF.

Inclusion Criteria:

• Males or females, ≥ 18 years of age, at Screening

• Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria, with at least 1 of the following: Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test OR Abnormal nasal transepithelial potential difference (NPD) test OR Two well-characterized, disease-causing genetic mutations in the CF transmembrane conductance regulator (CFTR) gene AND 1 or more accompanying clinical features consistent with CF

• FEV1 ≥ 40% and ≤ 90% predicted

• BMI ≥ 19 and ≤ 30 kg/m2

• Clinically stable with no evidence of significant new or acute respiratory symptoms

• Chest radiograph without significant acute findings; or chest radiograph, CT, or MRI obtained and interpreted within 90 days prior to enrollment, without acute findings and no significant intercurrent illness; chronic, stable findings are allowed

• History of lifetime smoking < 5 pack-years (ie, 1 pack per day x 1 year =

  1 pack-year) and non-smokers of at least 60 days duration prior to Screening

• Estimated creatinine clearance ≥ 80 mL/min at Screening

• Negative drug tests; including alcohol

• Hepatitis B, C, & HIV Negative

• Surgically sterile or ≥ 12 months post-menopausal

• Non-pregnant females

Exclusion Criteria:

• Experienced symptoms of recent acute upper or lower respiratory tract infection or acute pulmonary exacerbation requiring treatment within 2 weeks prior to Screening
• Plasma potassium ≥ 5 mEq/L
• Changes in chronic azithromycin use, bronchodilator (BD), dornase alfa, HS, physiotherapy technique or regimen, antibiotics or corticosteroid medications within 28 days prior to Screening
• History of sputum or throat swab culture yielding Burkholderia species within 2 years of Screening