TOPIC Trial for COPD

Early Phase 1

Completed

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Drug: Placebo
Drug: Ivacaftor

Registration Number: NCT02135432

Lead Sponsor: University of Alabama at Birmingham

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	matching placebo
Ivacaftor (VX-770)	Ivacaftor	twice a day administration of Ivacaftor: 150mg

Primary Outcome Measures

Name	Time	Method
Change in COPD as Measured by the Sweat Analysis in Each Group	baseline to 2 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Number of Adverse Events Experienced by the Ivacaftor Subjects and Placebo Subjects.	baseline to 2 weeks	Number of adverse events per subject in each the Ivacaftor subjects and placebo subjects
Change in COPD as Measured by Nasal Potential Difference	baseline to 2 weeks	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.
Change in COPD as Measured by Change in Percentage of FEV1 as Measured in Each Group	baseline to 2 weeks	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.