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TOPIC Trial for COPD

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ivacaftor
Placebo
Sponsored by
University of Alabama at Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring Chronic Obstructive pulmonary disease, Ivacaftor

Eligibility Criteria

40 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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Sites / Locations

  • University of Alabama at Birmingham

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ivacaftor (VX-770)

Placebo

Arm Description

twice a day administration of Ivacaftor: 150mg

matching placebo

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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
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.

Full Information

First Posted
April 15, 2014
Last Updated
January 5, 2017
Sponsor
University of Alabama at Birmingham
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1. Study Identification

Unique Protocol Identification Number
NCT02135432
Brief Title
TOPIC Trial for COPD
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
Chronic Obstructive pulmonary disease, Ivacaftor

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ivacaftor (VX-770)
Arm Type
Experimental
Arm Description
twice a day administration of Ivacaftor: 150mg
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
matching placebo
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Other Intervention Name(s)
Kalydeco
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change in COPD as Measured by the Sweat Analysis in Each Group
Description
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.
Time Frame
baseline to 2 weeks
Secondary Outcome Measure Information:
Title
Change in COPD as Measured by Nasal Potential Difference
Description
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.
Time Frame
baseline to 2 weeks
Title
Number of Adverse Events Experienced by the Ivacaftor Subjects and Placebo Subjects.
Description
Number of adverse events per subject in each the Ivacaftor subjects and placebo subjects
Time Frame
baseline to 2 weeks
Title
Change in COPD as Measured by Change in Percentage of FEV1 as Measured in Each Group
Description
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.
Time Frame
baseline to 2 weeks
Other Pre-specified Outcome Measures:
Title
Pharmacokinetics as Described by AUC12 of Subjects Receiving Ivacaftor
Time Frame
baseline to 2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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 -
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States

12. IPD Sharing Statement

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TOPIC Trial for COPD

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