Study of Ivacaftor in Subjects With Cystic Fibrosis Who Have the R117H-CFTR Mutation

Ivacaftor is the first cystic fibrosis transmembrane regulator (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

- Must have at least 1 allele of the R117H CFTR mutation

- FEV1 40% to 90% (for subjects aged 12 years or older) or 40% to 105% (for subjects
aged 6 to 11 years) 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:

- Any 1 of the following CFTR gating mutations: G551D, G178R, S549N, S549R, G551S,
G970R, G1244E, S1251N, S1255P, G1349D

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