Study of Ataluren in Nonsense Mutation Cystic Fibrosis (ACT CF)
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: Ataluren (PTC124®); Placebo
Intervention description: Oral Ataluren TID; Oral Placebo TID
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 279.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No

Summary:

      This is a Phase 3, international, multicenter, randomized, double-blind, placebo-controlled,
      efficacy and safety study of ataluren in patients with nonsense mutation cystic fibrosis
      (nmCF) not receiving chronic inhaled aminoglycosides.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

          -  Age >=6 years.

          -  Body weight >=16 kg.

          -  Sweat chloride >60 milliequivalent per liter (mEq/L)

          -  Documentation of the presence of a nonsense mutation in at least 1 allele of the
             cystic fibrosis transmembrane conductance regulator (CFTR) gene, as determined by
             genotyping performed at 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 sequencing of 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

          -  Demonstration at Visit 2 of a valid %-predicted FEV1 within 15% of the Screening %
             predicted FEV1 value

          -  Resting oxygen saturation (as measured by pulse oximetry) >=92% on room air.

          -  Confirmed screening laboratory values within pre-specified ranges

          -  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 60-day follow-up period

          -  Willingness and ability to comply with all study procedures and assessments, including
             scheduled visits, drug administration plan, study procedures, laboratory tests, and
             study restrictions

        Exclusion Criteria:

          -  Known hypersensitivity to any of the ingredients or excipients of the study drug

          -  Previous participation in the Phase 3 trial of ataluren (PTC124-GD-009-CF).

          -  Any change (initiation, change in type of drug, dose modification, schedule
             modification, interruption, discontinuation, or re-initiation) in a chronic
             treatment/prophylaxis regimen for Cystic Fibrosis (CF) or for CF-related conditions
             within 4 weeks prior to screening

          -  Chronic use of inhaled aminoglycosides (eg, tobramycin) or use of inhaled
             aminoglycosides within 4 weeks prior to screening.

          -  Exposure to another investigational drug within 4 weeks prior to screening

          -  Ongoing participation in any other therapeutic clinical trial

          -  Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection
             (including viral illnesses) within 3 weeks prior to screening

          -  Treatment with intravenous antibiotics within 3 weeks prior to screening

          -  Ongoing immunosuppressive therapy (other than corticosteroids)

          -  Ongoing warfarin, phenytoin, or tolbutamide therapy

          -  History of solid organ or hematological transplantation

          -  Major complications of lung disease (including massive hemoptysis, pneumothorax, or
             pleural effusion) within 8 weeks prior to screening

          -  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, electrocardiogram (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