Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis 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
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.