The purpose of this study is to investigate the safety, tolerability and pharmacokinetics of N6022, and to obtain descriptive information on the effect of N6022 on biomarkers of CFTR function and inflammation in adult cystic fibrosis subjects who are homozygous for the F508del-CFTR mutation.

This is a double-blind, randomized, placebo-controlled, multicenter, sequential dose-escalation study which will occur in two parts. All selection criteria, assessments and procedures described in this protocol will be applied to both parts. Up to 5 cohorts will be studied with a total of 67 patients at approximately 18 clinical sites in the United States.

Inclusion Criteria:

• Homozygous for F508del-CFTR gene
• Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis
• Body weight ≥ 40 kg
• FEV1 ≥ 40% predicted
• Oxygen saturation ≥ 90% breathing ambient air
• Hematology and clinical chemistry of blood and urine results with no clinically significant abnormalities that would interfere with the study assessments
• Negative pregnancy test for women of child bearing potential
• Sexually active subjects of child bearing potential willing to follow contraception requirements

Exclusion Criteria:

• Previous enrollment in another cohort for this study.
• Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment within 4 weeks of Study Day 1.
• Any change in chronic therapies for CF lung disease within 4 weeks of Study Day 1.
• Blood hemoglobin <10 g/dL at screening.
• Serum albumin <2.5 g/dL at screening.
• Abnormal liver function defined as ≥ 3 x upper limit of normal (ULN) in three or more of the following: AST, ALT, GGT, ALP, total bilirubin at screening.
• History of abnormal renal function (creatinine clearance < 50 mL/min using Cockcroft-Gault equation) within a year at screening.
• History, including the screening assessment, of ventricular tachycardia or other ventricular arrhythmias.
• History, including the screening assessment, of prolonged QT and/or QTcF interval (> 450 msec).
• History of solid organ or hematological transplantation.
• Intranasal medication changes within 14 days prior to Study Day 1
• Required Use of continuous (24 hr/d) or nocturnal supplemental oxygen.
• Concomitant use of any inhibitors or inducers of CYP3A4.