A Study of Ataluren in Pediatric Participants With Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: Ataluren
Intervention description: Ataluren will be provided as a vanilla-flavored powder to be mixed with water, milk, or apple juice. Participants are to receive a total of 42 doses of ataluren during each cycle, for a total of 84 doses of ataluren in both cycles.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 6 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Cystic fibrosis; Nonsense mutation; Premature stop codon

Summary:

      In some participants with cystic fibrosis (CF), the disease is caused by a nonsense mutation
      (premature stop codon) in the gene that makes the cystic fibrosis transmembrane regulator
      (CFTR) protein. Ataluren has been shown to partially restore CFTR production in animals with
      CF due to a nonsense mutation. The main purpose of this study is to understand whether
      ataluren can safely increase functional CFTR protein in the cells of participants with CF due
      to a nonsense mutation.
    

Eligibility criteria:

        Inclusion Criteria: Participants must meet all of the following conditions to be eligible
        for enrollment into the study:

          1. Diagnosis of CF based on conclusively abnormal sweat test (sweat chloride >35
             milliequivalents [mEq]/liter).

          2. Abnormal nasal epithelial TEPD total chloride conductance (a more electrically
             negative value than 5 mV for Δchloride-free+isoproterenol).

          3. Presence of a mutation in both alleles.

          4. Documentation that a blood sample has been drawn for reconfirmation of the presence of
             a nonsense mutation in the CFTR gene.

          5. Age ≥6 years.

          6. Body weight ≥25 kg.

          7. FEV1 ≥40% of predicted for age, gender, and height.

          8. Oxygen saturation ≥92% on room air.

          9. Willingness of male and female participants, 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.

         10. Negative pregnancy test (for females of childbearing potential).

         11. Willingness and ability to comply with scheduled visits, drug administration plan,
             study procedures (including TEPD measurements, clinical laboratory tests, pulmonary
             function tests, and PK sampling), and study restrictions.

         12. Ability to provide written informed consent and/or assent.

         13. Evidence of signed and dated informed consent document (by the participant or a legal
             guardian) indicating that the participant and/or the legal guardian has been informed
             of all pertinent aspects of the trial.

        Exclusion Criteria: The presence of any of the following conditions will exclude a
        participant from enrollment in the study:

          1. Prior exposure to ataluren.

          2. Prior or ongoing medical condition (for example, 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 participant, makes it unlikely that the course of treatment or follow-up
             would be completed, or could impair the assessment of study results.

          3. Ongoing acute illness including acute upper or lower respiratory infections within 2
             weeks before start of study treatment.

          4. History of major complications of lung disease (including recent massive hemoptysis or
             pneumothorax) within 2 months prior to start of study treatment.

          5. Abnormalities on screening chest x-ray suggesting clinically significant active
             pulmonary disease other than CF, or new, significant abnormalities such as atelectasis
             or pleural effusion which may be indicative of clinically significant active pulmonary
             involvement secondary to CF.

          6. Positive hepatitis B surface antigen, hepatitis C antibody test, or human
             immunodeficiency virus (HIV) test.

          7. Hemoglobin <10 grams/deciliter (g/dL).

          8. Serum albumin <2.5 g/dL.

          9. Abnormal liver function (serum total bilirubin > the upper limit of normal, or serum
             alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl
             transferase (GGT) >2.0 times the upper limit of normal).

         10. Abnormal renal function (serum creatinine >1.5 times upper limit of normal).

         11. Pregnancy or breast-feeding.

         12. History of solid organ or hematological transplantation.

         13. Exposure to another investigational drug within 14 days prior to start of study
             treatment.

         14. Ongoing participation in any other therapeutic clinical trial.

         15. Ongoing use of thiazolidinedione peroxisome proliferator-activated receptor gamma
             (PPAR γ) agonists, for example, rosiglitazone (Avandia® or equivalent) or pioglitazone
             (Actos® or equivalent).

         16. Change in intranasal medications (including use of corticosteroids, cromolyn,
             ipratropium bromide, phenylephrine, or oxymetazoline) within 14 days prior to start of
             study treatment.

         17. Change in treatment with systemic or inhaled corticosteroids within 14 days prior to
             start of study treatment.

         18. Use of or requirement for inhaled gentamicin or amikacin within 14 days prior to start
             of study treatment or during study treatment.

         19. Requirement for systemic aminoglycoside antibiotics within 14 days prior to start of
             study treatment.