This is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in people with CF who are homozygous for the F508del-CFTR mutation. This study is designed to evaluate the efficacy and safety of VX-661 in combination with ivacaftor. The active treatment regimen will be comprised of a morning dose of a fixed-dose combination tablet of 100 mg VX-661/150 mg ivacaftor once daily (qd) and an evening dose of ivacaftor 150 mg to be taken approximately 12 hours after the morning dose. The placebo regimen will be visually matched tablets to be taken with the same schedule as the active treatment.