Back to resultsA Study of the Effects of Lumacaftor/Ivacaftor (LUM/IVA) on Exercise Tolerance in Subjects With Cystic Fibrosis (CF), Homozygous for the F508del-CFTR Mutation
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
LUM/IVA
Placebo
Sponsored by
About this trial
This is an interventional other trial for Cystic Fibrosis
Eligibility Criteria
Inclusion Criteria:
- Homozygous for the F508del-CFTR mutation
- Confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis
- Stable CF disease as judged by the investigator
- Forced expiratory volume in 1 second (FEV1) at least 40% and not greater than 90% of predicted
Exclusion Criteria:
- History of any comorbidity that might confound the results of the study, interfere with the use of cardiopulmonary exercise tests (CPETs) as an assessment, or pose an additional risk in administering study drug to the subject
- Any previous exposure to LUM or IVA
- History of cardiac arrhythmia, ischemic heart disease, congestive heart failure, or other clinically significant cardiac condition, or medical condition requiring chronic use of a beta blocker, non-dihydropyridine calcium channel blocker, or other cardiac medication known to affect exercise tolerance
- History of solid organ or hematological transplantation
- For subjects under 18 years of age at Screening, except those who have had bilateral lens removal, selected findings on a screening ophthalmologic examination will be exclusionary
- Using or expected to require any concomitant medication that is prohibited in this study
- History of alcohol or drug abuse, as deemed by the investigator, in the past year, including but not limited to cannabis, cocaine, and opiates
- Participation in an investigational drug study within 30 days before the Screening Visit
- Pregnant or nursing females; males with a female partner who is pregnant or nursing
- Colonization with organisms associated with a more rapid decline in pulmonary status
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
LUM/IVA
Arm Description
Placebo matched to LUM/IVA fixed-dose combination tablet orally every 12 hours (q12h) for 24 weeks.
LUM 400 milligram (mg)/IVA 250 mg fixed-dose combination tablet orally q12h for 24 weeks.
Outcomes
Primary Outcome Measures
Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24
CPET was used to assess change in exercise tolerance, as measured by VO2max.
Secondary Outcome Measures
Relative (Percent) Change From Baseline in Exercise Duration During CPET at Week 24
Exercise duration is defined as the time at the termination of CPET exercise minus the corresponding time when CPET starts for each CPET exercise.
Absolute Change From Baseline in Exercise Duration During CPET at Week 24
Exercise duration is defined as the time at the termination of CPET exercise minus the corresponding time when CPET starts for each CPET exercise.
Absolute Change From Baseline in VO2max During CPET at Week 24
CPET was used to assess change in exercise tolerance, as measured by VO2max.
Absolute Change From Baseline in Oxygen Consumption (VO2) at Anaerobic Threshold at Week 24
Anaerobic threshold was defined as the exercise intensity at which lactate starts to accumulate.
Relative (Percent) Change From Baseline in VO2 at Anaerobic Threshold at Week 24
Anaerobic threshold was defined as the exercise intensity at which lactate starts to accumulate.
Absolute Change From Baseline in Functional VO2 Gain at Week 24
Relative (Percent) Change From Baseline in Functional VO2 Gain at Week 24
Absolute Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24
Relative (Percent) Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Relative (Percent) Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
BMI was defined as weight in kilograms (kg) divided by height in square meter (m^2).
Relative (Percent) Change From Baseline in BMI at Week 24
BMI was defined as weight in kg divided by height in m^2.
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24
The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life.
Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8)
The PHQ-8 is an eight item self-reported measure of depression. Each item is rated on a scale ranging from 0 (not at all) to 3 (nearly every day). Total score is the sum of individual eight items and ranges from 0 to 24, with higher scores indicating more severe depression symptoms. Total score of 0 to 5 indicates none to minimal depression, 6 to 10 indicates mild depression, 11 to 15 indicates moderate depression, 16 to 20 indicates moderately severe depression and 21 to 24 indicates severe depression.
Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores
The GAD-7 is a seven item, self-reported measurement of GAD severity. Each item is rated on a scale ranging from 0 (not at all) to 3 (nearly every day). Total score is the sum of individual seven items and ranges from 0 to 21, with higher scores indicating more severe anxiety symptoms. Total score of 0 to 5 indicates none to minimal anxiety, 6 to 10 indicates mild anxiety, 11 to 15 indicates moderate anxiety, 16 to 21 indicates severe anxiety.
Absolute Change From Baseline in Daily Physical Activity Counts as Determined by Actigraphy at Week 24
Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily physical activity counts.
Relative (Percent) Change From Baseline in Physical Activity as Determined by Actigraphy at Week 24
Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily physical activities.
Absolute Change From Baseline in Duration of Sleep Time at Week 24
Participants were provided with a wrist-worn actigraphy device which continuously collected data about sleep duration and quality.
Relative (Percent) Change From Baseline in Duration of Sleep Time at Week 24
Participants were provided with a wrist-worn actigraphy device which continuously collected data about sleep duration and quality.
Absolute Change From Baseline in Time Above Sedentary Duration at Week 24
Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily activities and sleep duration and quality.
Relative (Percent) Change From Baseline in Time Above Sedentary Duration at Week 24
Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily activities and sleep duration and quality.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Full Information
NCT ID
NCT02875366
First Posted
August 15, 2016
Last Updated
March 18, 2019
Sponsor
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT02875366
Brief Title
A Study of the Effects of Lumacaftor/Ivacaftor (LUM/IVA) on Exercise Tolerance in Subjects With Cystic Fibrosis (CF), Homozygous for the F508del-CFTR Mutation
Official Title
A Phase 4, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Study of the Effect of Lumacaftor/Ivacaftor Combination Therapy on Exercise Tolerance in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
September 2016 (Actual)
Primary Completion Date
September 2017 (Actual)
Study Completion Date
October 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase 4, randomized, double-blind, placebo-controlled, parallel-group study in subjects aged 12 years and older with CF who are homozygous for the F508del-CFTR mutation. This study is designed to evaluate the effect of LUM/IVA on exercise tolerance in subjects with CF, homozygous for the F508del-CFTR mutation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
7. Study Design
Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo matched to LUM/IVA fixed-dose combination tablet orally every 12 hours (q12h) for 24 weeks.
Arm Title
LUM/IVA
Arm Type
Experimental
Arm Description
LUM 400 milligram (mg)/IVA 250 mg fixed-dose combination tablet orally q12h for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
LUM/IVA
Other Intervention Name(s)
Lumacaftor/Ivacaftor
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24
Description
CPET was used to assess change in exercise tolerance, as measured by VO2max.
Time Frame
Baseline, Week 24
Secondary Outcome Measure Information:
Title
Relative (Percent) Change From Baseline in Exercise Duration During CPET at Week 24
Description
Exercise duration is defined as the time at the termination of CPET exercise minus the corresponding time when CPET starts for each CPET exercise.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Exercise Duration During CPET at Week 24
Description
Exercise duration is defined as the time at the termination of CPET exercise minus the corresponding time when CPET starts for each CPET exercise.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in VO2max During CPET at Week 24
Description
CPET was used to assess change in exercise tolerance, as measured by VO2max.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Oxygen Consumption (VO2) at Anaerobic Threshold at Week 24
Description
Anaerobic threshold was defined as the exercise intensity at which lactate starts to accumulate.
Time Frame
Baseline, Week 24
Title
Relative (Percent) Change From Baseline in VO2 at Anaerobic Threshold at Week 24
Description
Anaerobic threshold was defined as the exercise intensity at which lactate starts to accumulate.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Functional VO2 Gain at Week 24
Time Frame
Baseline, Week 24
Title
Relative (Percent) Change From Baseline in Functional VO2 Gain at Week 24
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24
Time Frame
Baseline, Week 24
Title
Relative (Percent) Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
Baseline, Week 24
Title
Relative (Percent) Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
Description
BMI was defined as weight in kilograms (kg) divided by height in square meter (m^2).
Time Frame
Baseline, Week 24
Title
Relative (Percent) Change From Baseline in BMI at Week 24
Description
BMI was defined as weight in kg divided by height in m^2.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24
Description
The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life.
Time Frame
Baseline, Week 24
Title
Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8)
Description
The PHQ-8 is an eight item self-reported measure of depression. Each item is rated on a scale ranging from 0 (not at all) to 3 (nearly every day). Total score is the sum of individual eight items and ranges from 0 to 24, with higher scores indicating more severe depression symptoms. Total score of 0 to 5 indicates none to minimal depression, 6 to 10 indicates mild depression, 11 to 15 indicates moderate depression, 16 to 20 indicates moderately severe depression and 21 to 24 indicates severe depression.
Time Frame
Baseline, Week 24
Title
Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores
Description
The GAD-7 is a seven item, self-reported measurement of GAD severity. Each item is rated on a scale ranging from 0 (not at all) to 3 (nearly every day). Total score is the sum of individual seven items and ranges from 0 to 21, with higher scores indicating more severe anxiety symptoms. Total score of 0 to 5 indicates none to minimal anxiety, 6 to 10 indicates mild anxiety, 11 to 15 indicates moderate anxiety, 16 to 21 indicates severe anxiety.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Daily Physical Activity Counts as Determined by Actigraphy at Week 24
Description
Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily physical activity counts.
Time Frame
Baseline, Week 24
Title
Relative (Percent) Change From Baseline in Physical Activity as Determined by Actigraphy at Week 24
Description
Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily physical activities.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Duration of Sleep Time at Week 24
Description
Participants were provided with a wrist-worn actigraphy device which continuously collected data about sleep duration and quality.
Time Frame
Baseline, Week 24
Title
Relative (Percent) Change From Baseline in Duration of Sleep Time at Week 24
Description
Participants were provided with a wrist-worn actigraphy device which continuously collected data about sleep duration and quality.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Time Above Sedentary Duration at Week 24
Description
Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily activities and sleep duration and quality.
Time Frame
Baseline, Week 24
Title
Relative (Percent) Change From Baseline in Time Above Sedentary Duration at Week 24
Description
Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily activities and sleep duration and quality.
Time Frame
Baseline, Week 24
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Day 1 up to Week 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Homozygous for the F508del-CFTR mutation
Confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis
Stable CF disease as judged by the investigator
Forced expiratory volume in 1 second (FEV1) at least 40% and not greater than 90% of predicted
Exclusion Criteria:
History of any comorbidity that might confound the results of the study, interfere with the use of cardiopulmonary exercise tests (CPETs) as an assessment, or pose an additional risk in administering study drug to the subject
Any previous exposure to LUM or IVA
History of cardiac arrhythmia, ischemic heart disease, congestive heart failure, or other clinically significant cardiac condition, or medical condition requiring chronic use of a beta blocker, non-dihydropyridine calcium channel blocker, or other cardiac medication known to affect exercise tolerance
History of solid organ or hematological transplantation
For subjects under 18 years of age at Screening, except those who have had bilateral lens removal, selected findings on a screening ophthalmologic examination will be exclusionary
Using or expected to require any concomitant medication that is prohibited in this study
History of alcohol or drug abuse, as deemed by the investigator, in the past year, including but not limited to cannabis, cocaine, and opiates
Participation in an investigational drug study within 30 days before the Screening Visit
Pregnant or nursing females; males with a female partner who is pregnant or nursing
Colonization with organisms associated with a more rapid decline in pulmonary status
Facility Information:
City
Melbourne
State/Province
Victoria
Country
Australia
City
Parkville
State/Province
Victoria
Country
Australia
City
Adelaide
Country
Australia
City
Camperdown
Country
Australia
City
Clayton
Country
Australia
City
Nedlands
Country
Australia
City
New Lambton Heights
Country
Australia
City
Randwick
Country
Australia
City
South Brisbane
Country
Australia
City
Subiaco
Country
Australia
City
Westmead
Country
Australia
City
Edinburgh
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
33358691
Citation
Wilson J, You X, Ellis M, Urquhart DS, Jha L, Duncan M, Tian S, Harris RA, Kotsimbos T, Keating D. VO2max as an exercise tolerance endpoint in people with cystic fibrosis: Lessons from a lumacaftor/ivacaftor trial. J Cyst Fibros. 2021 May;20(3):499-505. doi: 10.1016/j.jcf.2020.12.006. Epub 2020 Dec 24.
Results Reference
derived
Learn more about this trial
A Study of the Effects of Lumacaftor/Ivacaftor (LUM/IVA) on Exercise Tolerance in Subjects With Cystic Fibrosis (CF), Homozygous for the F508del-CFTR Mutation
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