TOPIC Trial for COPD

Study Overview
=================
Brief Summary
-----------------
The study is a randomized, double-blind, placebo-controlled, multiple-dose, pilot study of orally-administered ivacaftor in subjects with chronic obstructive pulmonary disease. Subjects will be administered the study drug ivacaftor 150 mg (or placebo) twice daily (BID).

Official Title
-----------------
A Randomized, Double-Blind, Placebo Controlled Pilot Study to Determine the Safety and Efficacy of Ivacaftor (VX-770) for the Treatment of Chronic Obstructive Pulmonary Disease (The TOPIC Trial)

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: Ivacaftor
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or Female age 40-65 A clinical diagnosis of COPD as defined by GOLD At Least a 10 pack year smoking history Exhibit symptoms of chronic bronchitis defined by MRC 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 Willing to monitor blood glucose if known history of diabetes mellitus requiring insulin or medical therapy Exclusion Criteria: Current Diagnosis of Asthma Daytime use of Oxygen Therapy 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 Cockcroft-Gault Any illness of abnormal lab finding that, in the opinion of the investigator or the subject's general practitioner, might confound the results of the study or pose an additional risk in administering study drug to the subject. Pregnant or Breastfeeding Subjects taking any inhibitors or inducers of CYP3A4, including certain herbal medications and grapefruit/grapefruit juice. Uncontrolled Diabetes Excluded medications and foods include the drugs and foods provided in the appendix document. Clinically significant arrhythmias or conduction abnormalities that in the opinion of the investigator affect patient safety have been added as exclusion criteria and criteria for withdrawal. Patients who have not been stable or have been hospitalized in the past 3 months with any clinically significant cardiac conditions. Subjects with history of cancer (current or past, unless remote (>5years))except for localized non-melanomatous skin cancers History of Stroke/CVA History of myocardial infarction/acute coronary syndrome Cardiac Failure NYHC grade III-IV Diabetes Type I Uncontrolled Hypertension Primary or secondary pulmonary hypertension -

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ivacaftor (VX-770)<br>twice a day administration of Ivacaftor: 150mg | Drug: Ivacaftor<br> <br> * Other names: Kalydeco;|
| Placebo Comparator: Placebo<br>matching placebo | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in COPD as Measured by the Sweat Analysis in Each Group | sweat analysis is measured by performing a sweat test in each participant. The primary analysis will compare the within group change in sweat chloride before (day 1) and after (day 14) ivacaftor or placebo administration and will be used to test the null hypothesis of no change in sweat chloride using a paired t-test unless the distributions are notably skewed, in which case the non-parametric Wilcoxon signed-rank test will be implemented due to small sample size. | baseline to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in COPD as Measured by Nasal Potential Difference | Evaluate the efficacy of ivacaftor treatment in patients with COPD including measures of CFTR activity and clinical outcome as measured by change in nasal potential difference measurement in each group. These data will be used to test the null hypothesis of no change in nasal potential difference (ΔLow Chloride plus isoproterenol) using a paired t-test unless the distributions are notably skewed, in which case the non-parametric Wilcoxon signed-rank test will be implemented due to small sample size. | baseline to 2 weeks | 
| Number of Adverse Events Experienced by the Ivacaftor Subjects and Placebo Subjects. | Number of adverse events per subject in each the Ivacaftor subjects and placebo subjects | baseline to 2 weeks | 
| Change in COPD as Measured by Change in Percentage of FEV1 as Measured in Each Group | Spirometry will be analyzed by ATS criteria, and the best of three reproducible efforts will be used to calculate FEV1 in comparison to Hankinson standards. The primary analysis will be the change in FEV1% from day 0 to day 14 within subject, and will be tested against the null hypothesis that no change occurs using a paired t-test unless the distributions are notably skewed, in which case the non-parametric Wilcoxon signed-rank test will be implemented due to small sample size. | baseline to 2 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Obstructive pulmonary disease, Ivacaftor