A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation

Inclusion Criteria: * Willing and able to use the delivery device as directed by the study manual. * Confirmed diagnosis of CF, defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis. * Homozygous for the F508del CFTR mutation. If the CFTR screening genotype result is not received before randomization, a previous CFTR genotype lab report may be used to establish eligibility. * Percent predicted forced expiratory volume at one second (FEV1) of ≥40 to \<90 percentage points adjusted for age, sex, and height according to the Global Lung Initiative (GLI) at the Screening Visit. * Willing to discontinue physician-prescribed saline use. * Female subjects of childbearing potential with a negative serum pregnancy test at the Screening Visit. Exclusion Criteria: * History of any comorbidity, which in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. * Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject. * An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug). * A 12 lead ECG demonstrating QTcF \>450 msec at the Screening Visit. * History of solid organ or hematological transplantation. * Used diuretics or renin-angiotensin aldosterone system antihypertensive drugs in the 28 days prior to Screening or an anticipated need for any of these medications during the study. * Ongoing or prior participation in an investigational drug study within 30 days of the Screening Visit. * Inability to withhold short-acting, long-acting, or once-daily, long-acting bronchodilator use for 4, 12, or 24 hours prior to clinic visit, respectively. * History of significant intolerance to inhaled saline, or intolerance to the single dose of saline at Screening * Known hypersensitivity or history of intolerance to Orkambi. * Pregnant and nursing females. * Subjects who have participated in Parion Sciences Study NCT02343445.