The goal of the study is to evaluate the safety and tolerability of P-1037 and to determine whether the combination of P-1037 with hypertonic saline or P-1037 alone has a greater effect on lung function in patients with CF than placebo (0.17% saline).

Inclusion Criteria:

• Male or female, 12 years of age or older.
• Diagnosis of cystic fibrosis as determined by the 1997 CF Consensus criteria (NIH Consensus Statement, 1997)
• Non-smoker
• FEV1 at Screening Visit 1 between 40% and 90%
• Stable regimen of CF medications and chest physiotherapy for the 28 days prior to Screening. Must be willing to discontinue use of hypertonic saline for the duration of the study.
• Clinically stable for at least 2 weeks
• All females of child-bearing potential must have a negative serum pregnancy test and if sexually active must agree to practice a highly effective form of contraception throughout the study and for 28 days after the last dose of study medication.

Exclusion Criteria:

• History of any organ transplantation or any significant disease or disorder

• Use of diuretics (including amiloride) or renin-angiotensin antihypertensive drugs or trimethoprim in the 28 days prior to Screening

• History of significant intolerance to inhaled hypertonic saline, as determined by the Investigator

• Known hypersensitivity to the study drug or amiloride

• Any clinically significant laboratory abnormalities at Screening Visit 1 as judged by the investigator, or any of the following:

  • Potassium ≥ 5 milliequivalent per Liter (mEq/L)
  • Abnormal renal function
  • Abnormal liver function, defined as ≥ 3 x upper limit of normal (ULN)
  • Hemoglobin level < 10.0 g/dL

• Female who is pregnant or lactating

• History of sputum or throat swab culture yielding Burkholderia species or Mycobacterium abscessus within 2 years of screening

• Has previously participated in an investigational trial involving administration of any investigational compound or use of an investigational device with 28 days prior to Screening

• Currently being treated with any ivacaftor containing regimen