PTC124 for Cystic Fibrosis

Inclusion Criteria: Diagnosis of CF based on documented evidence of a conclusively abnormal sweat test (sweat chloride >60 mEq/liter). Abnormal chloride secretion as measured by TEPD (a less than -5 mV TEPD assessment of chloride secretion with chloride-free amiloride and isoproterenol). Presence of a nonsense mutation in one of the alleles of the CFTR gene. Age ≥18 years. Body weight ≥40 kg. FEV1 ≥40% of predicted for age, gender, and height (Knudson standards). Oxygen saturation (as measured by pulse oximetry) ≥92% on room air. Willingness of male and female patients, if not surgically sterile, to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and follow-up periods. Negative pregnancy test (for females of childbearing potential). Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, and study restrictions. Ability to provide written informed consent. Exclusion Criteria: Prior or ongoing medical condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the patient, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results. Ongoing acute illness including acute upper or lower respiratory infections within 2 weeks before start of study treatment. History of major complications of lung disease within 2 months prior to start of study treatment. Abnormalities on screening chest x-ray suggesting clinically significant active pulmonary disease other than CF, or new, significant abnormalities that may be indicative of clinically significant active pulmonary involvement secondary to CF. Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test. Hemoglobin <10 g/dL. Serum albumin <2.5 g/dL. Abnormal liver function (serum ALT, AST, GGT, alkaline phosphatase, LDH, or total bilirubin > upper limit of normal). Abnormal renal function (serum creatinine >1.5 times upper limit of normal). Pregnancy or breast-feeding. History of solid organ or hematological transplantation. Exposure to another investigational drug within 14 days prior to start of study treatment. Ongoing participation in any other therapeutic clinical trial. Ongoing use of thiazolidinedione peroxisome proliferator-activated receptor gamma (PPAR γ) agonists, eg, rosiglitazone (Avandia® or equivalent) or pioglitazone (Actos® or equivalent) Change in intranasal medications (including use of corticosteroids, cromolyn, ipratropium bromide, phenylephrine, or oxymetazoline) within 14 days prior to start of study treatment. Change in treatment with systemic or inhaled corticosteroids within 14 days prior to start of study treatment. Use or requirement for inhaled gentamicin or amikacin within 14 days prior to start of study treatment or during study treatment. Requirement for systemic aminoglycoside antibiotics within 14 days prior to start of study treatment.