Evaluation of Ivacaftor in Patients Using Ataluren for Nonsense Mutations

In about 10% of patients with CF, the defect in the gene is known as a stop mutation. This
mutation truncates the cystic fibrosis transductive regulator (CFTR) protein production by
introducing a premature stop in the messenger RNA (mRNA), this type of mutation is known as a
stop mutation. Ataluren is a novel, oral drug that promotes this gene to work effectively and
readthrough that premature "stop sign". It is hypothesized that ivacaftor may increase the
efficacy of ataluren by activating a specific protein that may not be functioning properly.

Inclusion Criteria:

1. Evidence of signed and dated informed consent/assent document(s) indicating that the
subject (and/or his parent/legal guardian) has been informed of all pertinent aspects
of the trial.

2. Age ≥19 years

3. Body weight ≥16 kg

4. Diagnosis of cystic fibrosis and documentation of the presence of a nonsense mutations
of the CFTR gene, as determined by historical genotyping

5. Ability to perform a valid, reproducible spirometry with demonstration of a forced
expiratory volume in 1second (FEV1) ≥30% of predicted for age, gender, and height.

6. If the subject is sexually active, willingness to abstain from sexual intercourse or
employ a barrier or medical method of contraception during the study drug
administration

7. Willingness and ability to comply with all study procedures and assessments.

8. Currently receiving ataluren for nonsense mutations through other clinical trial
access.

Exclusion Criteria:

1. Any change (initiation, change in type of drug, dose modification, schedule
modification, interruption, discontinuation, or re-initiation) in a chronic
treatment/prophylaxis regimen for CF or for CF-related conditions within 2 weeks prior
to screening.

2. Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection
(including viral illnesses) within 2 weeks prior to screening.

3. Ongoing immunosuppressive therapy (other than corticosteroids up to 10mg/d equivalent
of prednisone)

4. Ongoing warfarin, phenytoin, or tolbutamide therapy.

5. History of solid organ or hematological transplantation.

6. A history of positive hepatitis B surface antigen test, hepatitis C antibody test, or
human immunodeficiency

7. Major complications of lung disease (including massive hemoptysis, pneumothorax, or
pleural effusion) within 4 weeks prior to screening.

8. Pregnancy or breast-feeding.

9. Current smoker or a smoking history of ≥10 pack-years (number of cigarette packs/day ×
number of years smoked).

10. Prior or ongoing medical condition (eg, renal failure, alcoholism, drug abuse,
psychiatric condition), medical history, physical findings, ECG findings, or
laboratory abnormality that, in the investigator's opinion, could adversely affect the
safety of the subject, makes it unlikely that the course of treatment or follow-up
would be completed, or could impair the assessment of study results.