PTC Study to Evaluate Ataluren in Combination With Ivacaftor

Cystic Fibrosis (CF) is a life threatening genetic disorder resulting from mutions found in
the CF gene known as the cystic fibrosis transmembrane conductance regulator or CFTR. This
defect prevents correct chloride absorption in and out of the cells The purpose of this study
is to explore the combination of ataluren and ivacaftor as a treatment for patients with a
specific cystic fibrosis mutation

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 ≥6 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% and ≤90% 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 being administered ivacaftor, either alone (Kalydeco) or in combination with
lumacaftor (Orkambi)

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. Ongoing participation in any other therapeutic clinical trial.

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

4. Ongoing inhaled tobramycin therapy.

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

6. Ongoing warfarin, phenytoin, or tolbutamide therapy.

7. History of solid organ or hematological transplantation.

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

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

10. Pregnancy or breast-feeding.

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

12. 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.