Study to Evaluate the Safety and Efficacy of CTP-656 in Patients With Cystic Fibrosis With CFTR Gating Mutations

This is a randomized, parallel-group, double-blind, placebo controlled multicenter study to
evaluate the safety and efficacy of CTP-656 in CF patients with CFTR gating mutations,
compared to Kalydeco, for a total of 28 days. Subjects will be randomized to receive either
double-blind CTP-656 or placebo, or open-label Kalydeco.

Inclusion Criteria:

- 18 years of age or older

- Has a confirmed diagnosis of CF with at least one allele of the following CFTR gating
mutations: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, and S549R.

- Has been stable on Kalydeco therapy for at least 3 months prior to screening

- Has FEV1 ≥ 60% of predicted normal for age, sex, and height at screening and baseline
(Day 1) assessments

- Weighs at least 40 kg at screening

- Patients of either gender and women of childbearing potential must be willing to use a
medically highly effective form of birth control during the treatment period and 30
days after the last dose of study treatment.

Exclusion Criteria:

- Acute upper respiratory infection or lower respiratory infection, pulmonary
exacerbation, or changes in therapy within 4 weeks of study treatment

- Uncontrolled type 2 diabetes, or uncontrolled CF-related diabetes

- History of hepatitis C or chronic active hepatitis B infection

- History of pulmonary tuberculosis, non-tuberculosis mycobacterial infections or
allergic bronchopulmonary aspergillosis (ABPA) treated during screening or within 2
years prior to screening

- Colonization with B. cenocepacia, B. dolosa, B. multivorans, and/or M. abcessus within
2 years prior to Screening

- Abnormal liver function

- History of abnormal renal function

- History of prolonged QTcF > 450 msec for males or QTcF > 470 msec for females

- History of solid organ or hematological transplantation

- Using any inhibitor or inducer of cytochrome P450/3A during the study or within 30
days of screening

- Women who are pregnant or lactating, or have plans to become pregnant during the study
or within 1 month following the last dose