Clearing Lungs With ENAC Inhibition in Cystic Fibrosis

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 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