A Phase 3 Rollover Study of Lumacaftor in Combination With Ivacaftor in Subjects 12 Years and Older With Cystic Fibrosis

This is a Phase 3, parallel group, multicenter, rollover study in subjects with CF who are
homozygous or heterozygous for the F508del CFTR mutation and who previously participated in
Study 103, Study 104, or Cohort 4 of Study 102

Inclusion Criteria:

- Signed informed consent form (ICF), and where appropriate, signed assent form.

- Subjects entering the Part A Treatment Cohort: Completed 24 weeks of study drug
treatment in Study 103 or Study 104 and elect to enroll in Part A treatment cohort.

- Subjects entering the Part B Treatment Cohort: Completed 56 days of study drug
treatment in Cohort 4 of Study 102 and elect to enroll in Part B treatment cohort.

- Subjects entering the Part A Observational Cohort: Completed 24 weeks of study drug
treatment in Study 103 or Study 104, but do not elect to enroll in the Part A
Treatment Cohort or do not qualify to enroll in Part A treatment cohort.

- Willing to remain on a stable CF medication regimen through the end of study (Part A
and Part B Treatment Cohorts only).

Exclusion Criteria:

- Any comorbidity or laboratory abnormality 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 subject (e.g., cirrhosis with portal hypertension).

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

- History of drug intolerance in the prior study that would pose an additional risk to
the subject in the opinion of investigator or Vertex.

- History of poor compliance with study drug and/or procedures in the previous study as
deemed by the investigator.

- Participation in an investigational drug trial (including studies investigating
lumacaftor and/or ivacaftor, or studies requiring blood collections with or without
administration of study drug)