Study of Ivacaftor in Subjects With Cystic Fibrosis Who Have a Non-G551D CFTR Gating Mutation

Ivacaftor is the first CFTR modulator to show an improvement in CFTR function and clinical
benefit in patients with CF. Results from Phase 3 studies (VX08-770-102 [Study 102] and
VX08-770-103 [Study 103]) showed that ivacaftor is effective in the treatment of patients
with CF who have the G551D-CFTR mutation, as evidenced by sustained improvements in CFTR
channel function (measured by reduction in sweat chloride concentration) and corresponding
substantial, durable improvements in lung function, pulmonary exacerbations, respiratory
symptoms, and weight gain. Ivacaftor was also well tolerated, as evidenced by the rates and
reasons for premature discontinuation and results of safety assessments.

Ivacaftor (Trade Name Kalydeco; 150 mg tablets) was initially approved in the United States
for the treatment of CF in patients 6 years of age and older who have a G551D mutation in
the CFTR gene.

Inclusion Criteria:

- Male or female with confirmed diagnosis of CF

- At least 1 allele of the following CFTR gating mutations: G178R, S549N, S549R, G551S,
G970R, G1244E, S1251N, S1255P, G1349D

- FEV1 ≥ 40% predicted normal for age, sex, and height

- 6 years of age or older

- Minimum weight of 15 kg at screening

- Females of childbearing potential must not be pregnant

- Willing to comply with contraception requirements

Exclusion Criteria:

- G551D-CFTR mutation on at least 1 allele

- History of any illness or condition that might confound the results of the study or
pose an additional risk in administering ivacaftor to the subject

- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in
therapy (including antibiotics) for pulmonary disease within 4 weeks before the first
dose of study drug

- History of solid organ or hematological transplantation

- History of alcohol, medication or illicit drug abuse within 1 year before the first
dose of study drug

- Ongoing participation in another therapeutic clinical study or prior participation in
an investigational drug study within 30 days before screening

- Use of inhaled hypertonic saline treatment

- Use of any inhibitors or inducers of cytochrome P450 (CYP) 3A