TOPIC Trial for COPD

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)

Status

Completed

Phases

Early Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02135432

Enrollment

Registered

2014-05-12

Start date

2015-05-31

Completion date

2015-11-30

Last updated

2017-02-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Chronic Obstructive pulmonary disease, Ivacaftor

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).

Interventions

DRUGIvacaftor

DRUGPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

40 Years to 65 Years

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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 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.

Other

Measure	Time frame
Pharmacokinetics as Described by AUC12 of Subjects Receiving Ivacaftor	baseline to 2 weeks

Countries

United States

Participant flow

Participants by arm

Arm	Count
Ivacaftor (VX-770) twice a day administration of Ivacaftor: 150mg Ivacaftor	8
Placebo matching placebo Placebo	4
Total	12

Baseline characteristics

Characteristic	Ivacaftor (VX-770)	Placebo	Total
Age, Continuous	55 years	62 years	55 years
Age, Customized <=18 years	0 participants	0 participants	0 participants
Age, Customized >=65 years	2 participants	1 participants	3 participants
Age, Customized Between 18 and 65 years	6 participants	3 participants	9 participants
Gender Female	4 Participants	1 Participants	5 Participants
Gender Male	4 Participants	3 Participants	7 Participants
Region of Enrollment United States	8 participants	4 participants	12 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	7 / 8	3 / 4
serious Total, serious adverse events	1 / 8	0 / 4

Outcome results

Primary

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.