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.
Name: Ivacaftor 150 MG
Name: Placebo
Description: Safety of ivacaftor will be determined by number of participants with adverse events (including serious adverse events).
Measure: Safety of ivacaftor - number of participants with adverse events Time: From Screening to Day 98Description: Number of participants with abnormal serum chemistry values compared to screening values will also be used to determine safety of ivacaftor.
Measure: Safety of ivacaftor - number of participants with abnormal serum chemistry Time: From Screening to Day 98Description: Safety of ivacaftor will also be determined by number of participants with abnormal changes in their screening hematology values.
Measure: Safety of ivacaftor - number of participants with abnormal hematology Time: From Screening to Day 98Description: Number of participants with abnormal changes in their screening ECGs is another factor that will be used to evaluate the safety of ivacaftor.
Measure: Safety of ivacaftor - number of participants with abnormal ECG Time: From Screening to Day 98Description: Clearance of Tc99 sulfur colloid is a measure of MCC of the lungs, and is calculated by a standard protocol developed by the Cystic Fibrosis Therapeutics Development Network. The method provides a robust measure of MCC, and has been sensitive to the effects of inhaled pharmacologic agents in CF and COPD including improvements of an unprecedentedly large magnitude in CF patients with the G551D-CFTR mutation treated with ivacaftor measured in a multicenter study. The technique allows estimates of MCC in both the small and large airway compartments.
Measure: Central CFTR activity measured by Mucociliary Clearance (MCC) Time: From Screening to Day 98Description: Sweat chloride abnormality is correlated with COPD severity and symptoms, and is a highly sensitive outcome measure for CFTR-directed therapeutics. We have shown sweat chloride is sensitive to the presence of cigarette smoking and COPD, and the test has been successfully used as an endpoint in multiple CF trials, including studies to detect the efficacy of ivacaftor therapy.
Measure: Peripheral CFTR activity measured by Sweat Chloride Time: From Screening to Day 98Description: Spirometry is a standard outcome measure in COPD and a major indicator of efficacy and safety in COPD clinical trials. Post-bronchodilator spirometry will be performed by ATS criteria. FEV1 will be measured in liters (L).
Measure: Indicators of respiratory function and COPD health : Change in FEV1 Time: From Screening to Day 98Description: Spirometry is a standard outcome measure in COPD and a major indicator of efficacy and safety in COPD clinical trials. Post-bronchodilator spirometry will be performed by ATS criteria. FVC will be measured in liters (L).
Measure: Indicators of respiratory function and COPD health : Change in FVC. Time: From Screening to Day 98Description: The SOBQ is a self-reported questionnaire that assesses shortness of breath while performing a variety of activities of daily living. The Minimum Clinically Important Difference (MCID) is 5.
Measure: San Diego Shortness of Breath Questionnaire (SOBQ) Time: From Screening to Day 98Description: The BCSS is a three-item questionnaire rating breathlessness, cough and sputum on a 5-point Likert scale from 0 (no symptoms) to 4 (severe symptoms).
Measure: Breathlessness, Cough, and Sputum Scale (BCSS) Time: From Screening to Day 98Description: CAT is a self reported questionnaire that measures COPD related quality of life. The MCID is 2.
Measure: COPD Assessment Test (CAT) Time: From Screening to Day 98Description: The SGRQ is a disease-specific measure of health status for use in COPD with an MCID of 4.
Measure: St. George Respiratory Questionnaire (SGRQ) Time: From Screening to Day 98Allocation: Randomized
Parallel Assignment
There is one SNP
The method provides a robust measure of MCC, and has been sensitive to the effects of inhaled pharmacologic agents in CF and COPD including improvements of an unprecedentedly large magnitude in CF patients with the G551D-CFTR mutation treated with ivacaftor measured in a multicenter study. --- G551D ---