Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: N6022; Normal saline
Intervention description: Intravenous solution of N6022 in normal saline administered by infusion pump over 1-8 minutes depending on the dose; Intravenous solution of 0.9% (weight/volume) NaCl administered by infusion pump over 1-8 minutes depending on dose of active drug used in same cohort
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cystic Fibrosis; F508del-CFTR; N6022; S-Nitrosoglutathione

Summary:

      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.
    

Eligibility criteria:

        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.