This will be a double-blind, randomized, placebo-controlled, parallel group study. The purpose of this study is to investigate the efficacy and safety of Cavosonstat (N91115) in adult patients with CF who are homozygous for the F508del-CFTR mutation and being treated with lumacaftor/ivacaftor (Orkambi™).

Primary Objective:

• Assess the efficacy of N91115 at 12 weeks when added to preexisting treatment with lumacaftor/ivacaftor in adult patients with CF who are homozygous for the F508del-CFTR mutation

Secondary Objectives:

• Assess the effect of N91115 added to lumacaftor/ivacaftor on safety
• Assess the effect of lumacaftor/ivacaftor added to N91115 on the pharmacokinetics of N91115, lumacaftor, and ivacaftor

Inclusion Criteria:

• Patients must have been treated with lumacaftor/ivacaftor for at least 8 weeks prior to Day 1 (start of dosing)
• A history of Sweat Chloride (SC) ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) (either before or after starting lumacaftor/ivacaftor treatment)
• Body weight ≥ 40 kg
• ppFEV1 40 - 85 % predicted (inclusive) at screening
• Oxygen saturation ≥ 90% breathing ambient air at screening

Exclusion Criteria:

• Any acute infection that requires treatment or hospitalization within 2 weeks of Study Day 1
• Colonization with organisms associated with more rapid decline in pulmonary status, such as Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus
• Any change in the regimen for chronic therapies for CF lung disease (e.g., Pulmozyme®, hypertonic saline, Azithromycin, TOBI®, Cayston®) within 4 weeks of Study Day 1
• Are pregnant, planning a pregnancy, or breast-feeding at screening
• 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)
• History of abnormal renal function within 3 months of screening
• History of ventricular tachycardia or other clinically significant ventricular arrhythmias
• History, including the screening assessment, of prolonged QT and/or QTcF (Fridericia's correction) interval
• History of solid organ or hematological transplantation
• History of alcohol abuse or drug abuse
• Ongoing participation in another therapeutic clinical trial
• Use of continuous (24 hr/day) or nocturnal supplemental oxygen