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 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.