Trial Outcomes & Findings for TOPIC Trial for COPD (NCT NCT02135432)

NCT ID: NCT02135432

Last Updated: 2017-02-24

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: EARLY_PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: baseline to 2 weeks
• Results posted on: 2017-02-24

Participant Flow

Participant milestones

Measure	Ivacaftor (VX-770) twice a day administration of Ivacaftor: 150mg Ivacaftor	Placebo matching placebo Placebo
Overall Study STARTED	8	4
Overall Study COMPLETED	8	4
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

TOPIC Trial for COPD

Baseline characteristics by cohort

Measure	Ivacaftor (VX-770) n=8 Participants twice a day administration of Ivacaftor: 150mg Ivacaftor	Placebo n=4 Participants matching placebo Placebo	Total n=12 Participants Total of all reporting groups
Age, Continuous	55 years n=5 Participants	62 years n=7 Participants	55 years n=5 Participants
Age, Customized <=18 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Age, Customized Between 18 and 65 years	6 participants n=5 Participants	3 participants n=7 Participants	9 participants n=5 Participants
Age, Customized >=65 years	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Gender Female	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Gender Male	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	4 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline to 2 weeks

Population: 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

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.

Outcome measures

Measure	Ivacaftor (VX-770) n=8 Participants twice a day administration of Ivacaftor: 150mg Ivacaftor	Placebo n=4 Participants matching placebo Placebo
Change in COPD as Measured by the Sweat Analysis in Each Group	-8.0 mmol/L Standard Deviation 4.4	2.0 mmol/L Standard Deviation 1.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Ivacaftor (VX-770) n=8 Participants twice a day administration of Ivacaftor: 150mg Ivacaftor	Placebo n=4 Participants matching placebo Placebo
Change in COPD as Measured by Nasal Potential Difference	-4.9 millivolts Standard Deviation 3.9	1.0 millivolts Standard Deviation 6.4

SECONDARY outcome

Timeframe: baseline to 2 weeks

Number of adverse events per subject in each the Ivacaftor subjects and placebo subjects

Outcome measures

Measure	Ivacaftor (VX-770) n=8 Participants twice a day administration of Ivacaftor: 150mg Ivacaftor	Placebo n=4 Participants matching placebo Placebo
Number of Adverse Events Experienced by the Ivacaftor Subjects and Placebo Subjects.	22 adverse events	14 adverse events

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Ivacaftor (VX-770) n=8 Participants twice a day administration of Ivacaftor: 150mg Ivacaftor	Placebo n=4 Participants matching placebo Placebo
Change in COPD as Measured by Change in Percentage of FEV1 as Measured in Each Group	-2.3 percentage of FEV1 Standard Deviation 5.2	1.8 percentage of FEV1 Standard Deviation 9.3

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline to 2 weeks

Outcome measures

Outcome data not reported

Adverse Events

Ivacaftor (VX-770)

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ivacaftor (VX-770) n=8 participants at risk twice a day administration of Ivacaftor: 150mg Ivacaftor	Placebo n=4 participants at risk matching placebo Placebo
Respiratory, thoracic and mediastinal disorders COPD Exacerbation	12.5% 1/8 • Number of events 1 • 1 year, 5 months	0.00% 0/4 • 1 year, 5 months

Other adverse events

Measure	Ivacaftor (VX-770) n=8 participants at risk twice a day administration of Ivacaftor: 150mg Ivacaftor	Placebo n=4 participants at risk matching placebo Placebo
Respiratory, thoracic and mediastinal disorders decreased/diminished breath sounds	50.0% 4/8 • Number of events 4 • 1 year, 5 months	75.0% 3/4 • Number of events 3 • 1 year, 5 months
Respiratory, thoracic and mediastinal disorders COPD Exacerbation	37.5% 3/8 • Number of events 3 • 1 year, 5 months	0.00% 0/4 • 1 year, 5 months
General disorders Headache	25.0% 2/8 • Number of events 2 • 1 year, 5 months	0.00% 0/4 • 1 year, 5 months
Gastrointestinal disorders Loose Stools	25.0% 2/8 • Number of events 2 • 1 year, 5 months	0.00% 0/4 • 1 year, 5 months

Additional Information

Steven M. Rowe

University of Alabama at Birmingham

Phone: 205-975-6385

Email: smrowe@uab.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place