The Topic Trial - Study to Determine the Safety and Efficacy of Ivacaftor
Condition: Chronic Obstructive Pulmonary Disease; Chronic Bronchitis
MeSH terms: Bronchitis; Bronchitis, Chronic; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Ivacaftor 150 MG; Placebo
Intervention description: Ivacaftor is a CFTR potentiator; placebo pills
Intervention MeSH terms: Ivacaftor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The design is a pilot, randomized (3:1, active:placebo), double-blind, placebo-controlled study
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: double-blind
Enrollment: 40.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: COPD; CFTR; ivacaftor; topic trial

Summary:

      The study is a Phase 2 Study to establish the safety and efficacy of a drug called Ivacaftor
      (VX-770) in patients with chronic obstructive pulmonary disease (COPD), chronic bronchitis,
      and acquired CFTR dysfunction as detected by sweat chloride analysis. The design is a pilot,
      randomized (3:1, active:placebo), double-blind, placebo-controlled study. Approximately 40
      subjects with COPD will be randomized.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or Female age 40-80

          -  A Clinical diagnosis of COPD as defined by GOLD

          -  At Least a 10 pack year smoking history

          -  Exhibit symptoms of chronic bronchitis as defined by the Medical Research Council

          -  FEV1% predicted ≥ 35% and ≤70% Post Bronchodilator

          -  Clinically stable in the last 4 weeks with no evidence of COPD exacerbation

          -  Weight of 40 kg-120 kg

          -  Willingness to use at least one form of acceptable birth control including abstinence,
             condom with spermicide, or hormonal contraceptives from time of signing ICF through
             study follow up visit

          -  Willing to monitor blood glucose if known history of diabetes mellitus requiring
             insulin or medical therapy

          -  Element of CFTR Dysfunction, as defined by Sweat Chloride > 30 mEq/L)

        Exclusion Criteria:

          -  Current Diagnosis of Asthma

          -  Known Diagnosis of Cystic Fibrosis

          -  Use of Continuous Oxygen Therapy of greater than 2 liters per minute - patients on 2
             liters of Oxygen or less will be excluded if they have been hospitalized for COPD in
             the prior year or had more than 2 exacerbations requiring steroids and/or antibiotics
             in the prior year.

          -  Documented history of drug abuse within the last year

          -  Subjects should not have a pulmonary exacerbation or changes in therapy for pulmonary
             disease within 28 days before receiving the first dose of study drug.

          -  Cirrhosis or elevated liver transaminases > 3X ULN

          -  GFR < 50 estimated by Cockroft-Gault

          -  Any illness or abnormal lab finding that, in the opinion of the investigator might
             confound the results of the study or pose an additional risk in administering study
             drug to the subject.

          -  Pregnant or Breastfeeding

          -  Subjects taking moderate or strong inhibitors or inducers of CYP3A4, including certain
             herbal medications and grapefruit juice. (Excluded medications and foods including the
             drugs and foods listed in the IRB HSP application.)

          -  Uncontrolled Diabetes

          -  Recent (e.g 1year) arterial thrombotic events (peripheral arterial disease, thrombotic
             stroke)

          -  Clinically significant arrhythmias requiring anti-arrhythmic agent(s) or conduction
             abnormalities that in the opinion of the investigator that affect patient safety such
             as the abnormalities listed below (patients with stable coronary artery disease are
             eligible) : (1) Angina symptoms (2) History of MI (3) Revascularization procedure in
             the last year prior to screening (4) Clinically significant congestive heart failure
             (known LVEF <= 45%, cor pulmonale, diastolic heart failure, etc)