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)
Overview
- Phase
- Early Phase 1
- Intervention
- Ivacaftor
- Conditions
- Chronic Obstructive Pulmonary Disease
- Sponsor
- University of Alabama at Birmingham
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Change in COPD as Measured by the Sweat Analysis in Each Group
- Status
- Completed
- Last Updated
- 9 years ago
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).
Investigators
Dr. Steven M Rowe
MD
University of Alabama at Birmingham
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
Arms & Interventions
Ivacaftor (VX-770)
twice a day administration of Ivacaftor: 150mg
Intervention: Ivacaftor
Placebo
matching placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Change in COPD as Measured by the Sweat Analysis in Each Group
Time Frame: 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 Outcomes
- Number of Adverse Events Experienced by the Ivacaftor Subjects and Placebo Subjects.(baseline to 2 weeks)
- Change in COPD as Measured by Nasal Potential Difference(baseline to 2 weeks)
- Change in COPD as Measured by Change in Percentage of FEV1 as Measured in Each Group(baseline to 2 weeks)