Study of Ataluren (PTC124™) in Cystic Fibrosis

Inclusion Criteria:

• Ability to provide written informed consent (parental/guardian consent and subject assent if <18 years of age)
• Age ≥6 years
• Body weight ≥16 kg
• Abnormal nasal TEPD total chloride conductance (a less electrically negative value than -5 mV for total chloride conductance [Δchloride-free+isoproterenol])
• Sweat chloride >40 mEq/L
• Documentation of the simultaneous presence of a nonsense mutation in at least 1 allele of the CFTR gene and a CF-causing mutation in the other CFTR allele, as determined by gene sequencing from a laboratory certified by the College of American Pathologists (CAP), or under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an equivalent organization
• Verification that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the CFTR gene
• Ability to perform a valid, reproducible spirometry test using the study-specific spirometer with demonstration of an FEV1 ≥40% and ≤90% of predicted for age, gender, and height
• Resting oxygen saturation (as measured by pulse oximetry) ≥92% on room air
• Documentation by VivoMetrics that the subject has satisfactorily completed a 24-hour LifeShirt® cough frequency assessment
• Confirmed screening laboratory values within the central laboratory ranges (hepatic, adrenal, renal, serum electrolytes, and reproduction [women only] parameters)
• In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 4-week follow-up period
• Willingness and ability to comply with scheduled visits, drug administration plan, study restrictions, and study procedures

Exclusion Criteria:

• Known hypersensitivity to any of the ingredients or excipients of the study drug
• Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or reinitiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to start of study treatment
• Exposure to another investigational drug within 4 weeks prior to start of study treatment
• Treatment with systemic aminoglycoside antibiotics at the time of the baseline TEPD assessment
• Treatment with intravenous antibiotics within 3 weeks prior to start of study treatment
• History of solid organ or hematological transplantation
• Ongoing immunosuppressive therapy (other than corticosteroids)
• Ongoing warfarin, phenytoin, or tolbutamide therapy
• Ongoing participation in any other therapeutic clinical trial
• Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 8 weeks prior to start of study treatment
• Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to randomization
• Known portal hypertension
• Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test
• Pregnancy or breast-feeding
• Current smoker or a smoking history of ≥10 pack-years (number of cigarette packs/day x number of years smoked)
• Prior or ongoing medical condition (eg, concomitant illness, 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