Trial Outcomes & Findings for The Topic Trial - Study to Determine the Safety and Efficacy of Ivacaftor (NCT NCT03085485)

NCT ID: NCT03085485

Last Updated: 2024-12-12

Results Overview

Safety of ivacaftor will be determined by number of participants with adverse events (including serious adverse events).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: From Screening to Day 98
• Results posted on: 2024-12-12

Participant Flow

Participant milestones

Measure	Ivacaftor Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo matching placebo Placebo: placebo pills
Overall Study STARTED	30	10
Overall Study COMPLETED	28	10
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	Ivacaftor Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo matching placebo Placebo: placebo pills
Overall Study Death	1	0
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

The Topic Trial - Study to Determine the Safety and Efficacy of Ivacaftor

Baseline characteristics by cohort

Measure	Ivacaftor n=30 Participants Ivacaftor, 150 mg PO BID for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 Participants matching placebo Placebo: placebo pills	Total n=40 Participants Total of all reporting groups
Age, Continuous	65.3 years STANDARD_DEVIATION 7.9 • n=5 Participants	65.9 years STANDARD_DEVIATION 5.3 • n=7 Participants	65.5 years STANDARD_DEVIATION 7.3 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	6 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	4 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	4 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	6 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Body Mass Index	27.6 kg/m^2 STANDARD_DEVIATION 5.7 • n=5 Participants	28.0 kg/m^2 STANDARD_DEVIATION 5.3 • n=7 Participants	27.7 kg/m^2 STANDARD_DEVIATION 5.6 • n=5 Participants
Current Smoker	20 Participants n=5 Participants	4 Participants n=7 Participants	24 Participants n=5 Participants
Smoking Exposure	41.3 pack/year STANDARD_DEVIATION 25.2 • n=5 Participants	27.8 pack/year STANDARD_DEVIATION 15.4 • n=7 Participants	38.0 pack/year STANDARD_DEVIATION 22.7 • n=5 Participants

PRIMARY outcome

Timeframe: From Screening to Day 98

Population: One subject dropped out of study after being randomized.

Safety of ivacaftor will be determined by number of participants with adverse events (including serious adverse events).

Outcome measures

Measure	Ivacaftor n=29 Participants Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 Participants matching placebo Placebo: placebo pills
Safety of Ivacaftor - Number of Participants With Adverse Events Subject with any AE	19 Participants	6 Participants
Safety of Ivacaftor - Number of Participants With Adverse Events AE resulting in drug interruption	7 Participants	3 Participants
Safety of Ivacaftor - Number of Participants With Adverse Events AE resulting in drug discontinuation	1 Participants	1 Participants

PRIMARY outcome

Timeframe: From Screening to Day 98

Number of participants with abnormal serum chemistry values compared to screening values will also be used to determine safety of ivacaftor.

Outcome measures

Measure	Ivacaftor n=29 Participants Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 Participants matching placebo Placebo: placebo pills
Safety of Ivacaftor - Number of Participants With Abnormal Serum Chemistry	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From Screening to Day 98

Safety of ivacaftor will also be determined by number of participants with abnormal changes in their screening hematology values.

Outcome measures

Measure	Ivacaftor n=29 Participants Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 Participants matching placebo Placebo: placebo pills
Safety of Ivacaftor - Number of Participants With Abnormal Hematology	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From Screening to Day 98

Number of participants with abnormal changes in their screening ECGs is another factor that will be used to evaluate the safety of ivacaftor.

Outcome measures

Measure	Ivacaftor n=29 Participants Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 Participants matching placebo Placebo: placebo pills
Safety of Ivacaftor - Number of Participants With Abnormal ECG (Prolonged QT Intervals)	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From Screening to Day 84

Clearance of Tc99 sulfur colloid is a measure of MCC of the lungs, and is calculated by a standard protocol developed by the Cystic Fibrosis Therapeutics Development Network. The method provides a robust measure of MCC, and has been sensitive to the effects of inhaled pharmacologic agents in CF and COPD including improvements of an unprecedentedly large magnitude in CF patients with the G551D-CFTR mutation treated with ivacaftor measured in a multicenter study. The technique allows estimates of MCC in both the small and large airway compartments.

Outcome measures

Measure	Ivacaftor n=29 Participants Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 Participants matching placebo Placebo: placebo pills
Central CFTR Activity Measured by Mucociliary Clearance (MCC) Percentage Clearance at 60 Mins Screening	88.4 percentage of clearance Standard Deviation 12	86.2 percentage of clearance Standard Deviation 7
Central CFTR Activity Measured by Mucociliary Clearance (MCC) Percentage Clearance at 60 Mins Day 84	86 percentage of clearance Standard Deviation 17	80 percentage of clearance Standard Deviation 2

SECONDARY outcome

Timeframe: From Screening to Day 84

Sweat chloride abnormality is correlated with COPD severity and symptoms, and is a highly sensitive outcome measure for CFTR-directed therapeutics. We have shown sweat chloride is sensitive to the presence of cigarette smoking and COPD, and the test has been successfully used as an endpoint in multiple CF trials, including studies to detect the efficacy of ivacaftor therapy.

Outcome measures

Measure	Ivacaftor n=30 Participants Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 Participants matching placebo Placebo: placebo pills
Peripheral CFTR Activity Measured by Change in Sweat Chloride	3.9 mmol/L Standard Deviation 9.8	3.8 mmol/L Standard Deviation 12.1

SECONDARY outcome

Timeframe: From Screening to Day 84

Spirometry is a standard outcome measure in COPD and a major indicator of efficacy and safety in COPD clinical trials. Post-bronchodilator spirometry will be performed by ATS criteria. FEV1 will be measured in predict percentage.

Outcome measures

Measure	Ivacaftor n=29 Participants Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 Participants matching placebo Placebo: placebo pills
Indicators of Respiratory Function and COPD Health : Change in FEV1 Predict %	1.5 predict percentage Standard Deviation 4.7	-0.4 predict percentage Standard Deviation 7.6

SECONDARY outcome

Timeframe: From D1 to Day 84

The SOBQ is a self-reported questionnaire that assesses shortness of breath while performing a variety of activities of daily living. The Minimum Clinically Important Difference (MCID) is 5.

The SOBQ includes 24 items, using 6-point scale with 0 = "not at all" to 5 = "maximal or unable to do because of breathlessness". The sum of SOBQ score ranges from 0 to 120, with higher score indicating more breathlessness.

Outcome measures

Measure	Ivacaftor n=29 Participants Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 Participants matching placebo Placebo: placebo pills
San Diego Shortness of Breath Questionnaire (SOBQ)	-6.25 units on a scale Standard Deviation 26.8	-8.6 units on a scale Standard Deviation 12.2

SECONDARY outcome

Timeframe: From D1 to Day 84

The BCSS is a three-item questionnaire rating breathlessness, cough and sputum on a 5-point Likert scale from 0 (no symptoms) to 4 (severe symptoms).

The BCSS score ranges from 0 to 12; the higher the score indicates the worse of symptoms.

Outcome measures

Measure	Ivacaftor n=29 Participants Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 Participants matching placebo Placebo: placebo pills
Breathlessness, Cough, and Sputum Scale (BCSS)	-0.6 units on a scale Standard Deviation 2.8	-1.2 units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: From D1 to Day 84

CAT is a self-reported questionnaire that measures COPD related quality of life. The MCID is 2.

CAT composes of 8 questions, and the scores range from 0 - 40. Higher scores denote a more severe impact of COPD on a patient's life.

Outcome measures

Measure	Ivacaftor n=29 Participants Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 Participants matching placebo Placebo: placebo pills
COPD Assessment Test (CAT)	-0.7 units on a scale Standard Deviation 6.9	-1 units on a scale Standard Deviation 6.7

SECONDARY outcome

Timeframe: From D1 to Day 84

The SGRQ is a disease-specific measure of health status for use in COPD with an MCID of 4.

The scores range from 0 to 100, with higher scores indicating more limitations.

Outcome measures

Measure	Ivacaftor n=29 Participants Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 Participants matching placebo Placebo: placebo pills
St. George Respiratory Questionnaire (SGRQ)	-7.6 score on a scale Standard Deviation 21.0	-10.1 score on a scale Standard Deviation 10.6

Adverse Events

Ivacaftor

Serious events: 6 serious events

Other events: 0 other events

Deaths: 19 deaths

Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 6 deaths

Serious adverse events

Measure	Ivacaftor n=29 participants at risk Ivacaftor, 150 mg PO every 12 hrs for 84 days Ivacaftor 150 MG: Ivacaftor is a CFTR potentiator	Placebo n=10 participants at risk matching placebo Placebo: placebo pills
Respiratory, thoracic and mediastinal disorders Pneumonia	6.9% 2/29 • Number of events 2 • Screening to Day 98	0.00% 0/10 • Screening to Day 98
Psychiatric disorders Altered mental status	3.4% 1/29 • Number of events 1 • Screening to Day 98	0.00% 0/10 • Screening to Day 98
Gastrointestinal disorders Diarrhea	3.4% 1/29 • Number of events 1 • Screening to Day 98	0.00% 0/10 • Screening to Day 98
Respiratory, thoracic and mediastinal disorders AECOPD	6.9% 2/29 • Number of events 2 • Screening to Day 98	0.00% 0/10 • Screening to Day 98
Respiratory, thoracic and mediastinal disorders Chest pain	0.00% 0/29 • Screening to Day 98	10.0% 1/10 • Number of events 1 • Screening to Day 98

Other adverse events

Adverse event data not reported

Additional Information

Bo Liu

University of Alabama at Birmingham

Phone: (205) 975-7868

Email: boliu@uabmc.edu

Results disclosure agreements

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