TOPIC Trial for COPD

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Completed
• CT.gov ID: NCT02135432
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 6
• Patients Per Site Per Month: 2

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Ivacaftor; Drug: Placebo	Early Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: May 1, 2015
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ivacaftor (VX-770) twice a day administration of Ivacaftor: 150mg	Drug: Ivacaftor; Other Names: Kalydeco
Placebo Comparator: Placebo matching placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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

3. 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 Outcome Measures

1. Pharmacokinetics as Described by AUC12 of Subjects Receiving Ivacaftor [baseline to 2 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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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Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233

Sponsors and Collaborators

• University of Alabama at Birmingham

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Steven M Rowe, MD, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT02135432
• Other Study ID Numbers: F140319002; TOPIC Trial
• First Posted: May 12, 2014
• Last Update Posted: Feb 24, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Dr. Steven M Rowe, MD, University of Alabama at Birmingham: Chronic Obstructive pulmonary disease, Ivacaftor
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Ivacaftor

Study Results

Participant Flow

Arm/Group Title	Ivacaftor (VX-770)	Placebo
Arm/Group Description	twice a day administration of Ivacaftor: 150mg Ivacaftor	matching placebo Placebo
Period Title: Overall Study
STARTED	8	4
COMPLETED	8	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ivacaftor (VX-770)	Placebo	Total
Arm/Group Description	twice a day administration of Ivacaftor: 150mg Ivacaftor	matching placebo Placebo	Total of all reporting groups
Overall Participants	8	4	12
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	55	62	55
Age, Customized (participants) [Number]
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 75%	3 75%	9 75%
>=65 years	2 25%	1 25%	3 25%
Gender (Count of Participants)
Female	4 50%	1 25%	5 41.7%
Male	4 50%	3 75%	7 58.3%
Region of Enrollment (participants) [Number]
United States	8 100%	4 100%	12 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

8 patients were analyzed in the ivacaftor Arm because 8 patients were randomized to study drug and only 4 patients were randomized in the placebo arm because 4 patients received placebl

Arm/Group Title	Ivacaftor (VX-770)	Placebo
Arm/Group Description	twice a day administration of Ivacaftor: 150mg Ivacaftor	matching placebo Placebo
Measure Participants	8	4
Mean (Standard Deviation) [mmol/L]	-8.0 (4.4)	2.0 (1.5)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ivacaftor	Placebo
Arm/Group Description	patients randomized to ivacaftor twice daily	matching placebo Placebo
Measure Participants	8	4
Mean (Standard Deviation) [millivolts]	-4.9 (3.9)	1.0 (6.4)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ivacaftor (VX-770)	Placebo
Arm/Group Description	twice a day administration of Ivacaftor: 150mg Ivacaftor	matching placebo Placebo
Measure Participants	8	4
Number [adverse events]	22	14

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ivacaftor (VX-770)	Placebo
Arm/Group Description	twice a day administration of Ivacaftor: 150mg Ivacaftor	matching placebo Placebo
Measure Participants	8	4
Mean (Standard Deviation) [percentage of FEV1]	-2.3 (5.2)	1.8 (9.3)

5. Other Pre-specified Outcome

Title	Pharmacokinetics as Described by AUC12 of Subjects Receiving Ivacaftor
Time Frame	baseline to 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	1 year, 5 months
Arm/Group Title	Ivacaftor (VX-770)		Placebo
Arm/Group Description	twice a day administration of Ivacaftor: 150mg Ivacaftor		matching placebo Placebo
All Cause Mortality
	Ivacaftor (VX-770)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ivacaftor (VX-770)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
COPD Exacerbation	1/8 (12.5%)	1	0/4 (0%)	0
Other (Not Including Serious) Adverse Events
	Ivacaftor (VX-770)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/8 (87.5%)		3/4 (75%)
Gastrointestinal disorders
Loose Stools	2/8 (25%)	2	0/4 (0%)	0
General disorders
Headache	2/8 (25%)	2	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
decreased/diminished breath sounds	4/8 (50%)	4	3/4 (75%)	3
COPD Exacerbation	3/8 (37.5%)	3	0/4 (0%)	0

Limitations/Caveats

this pilot trial was under powered and potentially too brief to detect definitive changes in lung function

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.