Safety Study of Ivacaftor in Subjects With Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: Ivacaftor 25 mg/75 mg; Ivacaftor 75 mg/150 mg; Ivacaftor 150 mg or 250 mg; Placebo
Intervention description: 25 mg or 75 mg q12h for a total of 28 days (Part 1); 75 mg or 150 mg q12h for a total of 28 days (Part 1); 150 mg or 250 mg of ivacaftor q12h for 28 days (Part 2); Given q12h for 28 days each in Part 1 and Part 2 of the study
Intervention MeSH terms: Ivacaftor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: G551D mutation; Fibrosis; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Pathologic Processes

Summary:

      The purpose of this study was to evaluate the safety and tolerability of ivacaftor in
      patients with cystic fibrosis (CF) who were aged 18 years or older and have a G551D mutation
      in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a potent
      and selective CFTR potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR
      protein. Potentiators are pharmacological agents that increase the chloride ion transport
      properties of the channel in the presence of cyclic AMP-dependent protein kinase A (PKA)
      activation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Weighing at least 40 kg

          -  Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele

          -  Forced expiratory volume in 1 second (FEV1) of at least 40% of predicted normal for
             age, gender, and height

          -  Willing to remain on stable medication regimen for the duration of study participation

          -  No significant clinical laboratory abnormalities, not pregnant, and willing to use at
             least 2 highly effective birth control methods during Part 1 and 1 highly effective
             birth control method during Part 2 of the study

          -  No clinically significant abnormalities that would have interfered with the study
             assessments, as judged by the investigator

        Exclusion Criteria:

          -  History of any illness or condition that might confound the results of the study or
             pose an additional risk in administering study drug to the subject

          -  Ongoing acute respiratory infection, pulmonary exacerbation, or changes in therapy for
             pulmonary disease within 14 days of Day 1 of the study

          -  History of alcohol, medication or illicit drug abuse within one year prior to Day 1

          -  Abnormal liver function ≥ 3x the upper limit of normal

          -  History of abnormal renal function (creatinine clearance < 50 mL/min using
             Cockcroft-Gault equation)

          -  History of solid organ or hematological transplantation

          -  Pregnant or breast-feeding (for women)

          -  Ongoing participation in another therapeutic clinical trial, or prior participation in
             an investigational drug study without appropriate washout

          -  Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP3A4)