Study to Evaluate Lumacaftor and Ivacaftor Combination Therapy in Subjects 12 Years and Older With Advanced Lung Disease

Inclusion Criteria:

- Homozygous for the F508del-CFTR mutation; historical genotype must be documented in
the participant's source documents.

- Percent predicted FEV1 <40 of adjusted for age, sex, and height at Screening

Exclusion Criteria:

- Participant currently receiving invasive mechanical ventilation.

- History of any comorbidity that, in the opinion of the investigator, might confound
the results of the study or pose an additional risk in administering study drug to the
participant

- Any clinically significant laboratory abnormalities at screening that would interfere
with the study assessments or pose an undue risk for the subject

- A 12-lead electrocardiograms (ECG) demonstrating QTcF >450 msec at Screening

- History of solid organ or hematological transplantation

- History of alcohol or drug abuse in the past year

- Ongoing or prior participation in an investigational drug study (including studies
investigating lumacaftor and/or ivacaftor) within 30 days of screening.

- Use of strong inhibitors, moderate inducers, or strong inducers of CYP3A

- Pregnant and nursing females: Females of childbearing potential must have a negative
pregnancy test at Screening and Day 1.

- Sexually active subjects of reproductive potential who are not willing to follow the
contraception requirements

- Use of beta blockers or the equivalent at Screening.