Phase 4
Completed N=70
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
Source: ClinicalTrials.gov NCT02875366 ↗Enrolled (actual)
70
Serious AEs
34.3%
Results posted
Jun 2019
Primary outcomePrimary: Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24 — -3.5; -6.6 percent change — p=0.3021
◆ Published Evidence
Established
23citations · ~5 / year
VO<sub>2max</sub> as an exercise tolerance endpoint in people with cystic fibrosis: Lessons from a lumacaftor/ivacaftor trial.
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.
Linked Publications
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VO<sub>2max</sub> as an exercise tolerance endpoint in people with cystic fibrosis: Lessons from a lumacaftor/ivacaftor trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24 |
-3.5; -6.6 | 0.3021 |
| SECONDARY Relative (Percent) Change From Baseline in Exercise Duration During CPET at Week 24 |
0.4; -2.8 | 0.1894 |
| SECONDARY Absolute Change From Baseline in Exercise Duration During CPET at Week 24 |
-2.1; -17.4 | 0.2328 |
| SECONDARY Absolute Change From Baseline in VO2max During CPET at Week 24 |
-1.3; -2.7 | 0.1203 |
| SECONDARY Absolute Change From Baseline in Oxygen Consumption (VO2) at Anaerobic Threshold at Week 24 |
94.6; -55.1 | 0.0439 sig |
| SECONDARY Relative (Percent) Change From Baseline in VO2 at Anaerobic Threshold at Week 24 |
9.4; 1.8 | 0.2237 |
| SECONDARY Absolute Change From Baseline in Functional VO2 Gain at Week 24 |
0.07; -0.53 | 0.0226 sig |
| SECONDARY Relative (Percent) Change From Baseline in Functional VO2 Gain at Week 24 |
1.46; -4.85 | 0.0613 |
| SECONDARY Absolute Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24 |
0.5; 0.8 | 0.6409 |
| SECONDARY Relative (Percent) Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24 |
2.0; 3.0 | 0.5889 |
| SECONDARY Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 |
-4.0; -0.6 | 0.1460 |
| SECONDARY Relative (Percent) Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 |
-5.4; -1.8 | 0.3091 |
| SECONDARY Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 |
0.3; 0.5 | 0.3961 |
| SECONDARY Relative (Percent) Change From Baseline in BMI at Week 24 |
1.5; 2.5 | 0.3905 |
| SECONDARY Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24 |
-6.1; 0.1 | 0.1257 |
| SECONDARY Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) |
27; 28; 8; 5; 0; 1 | — |
| SECONDARY Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores |
31; 29; 5; 5; 0; 0 | — |
| SECONDARY Absolute Change From Baseline in Daily Physical Activity Counts as Determined by Actigraphy at Week 24 |
-23239; -22409 | — |
| SECONDARY Relative (Percent) Change From Baseline in Physical Activity as Determined by Actigraphy at Week 24 |
-5; -7 | — |
| SECONDARY Absolute Change From Baseline in Duration of Sleep Time at Week 24 |
-0.4; 0.1 | — |
| SECONDARY Relative (Percent) Change From Baseline in Duration of Sleep Time at Week 24 |
-5.7; 1.5 | — |
| SECONDARY Absolute Change From Baseline in Time Above Sedentary Duration at Week 24 |
-0.7; -0.7 | — |
| SECONDARY Relative (Percent) Change From Baseline in Time Above Sedentary Duration at Week 24 |
0.2; 2.3 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
35; 30; 9; 15 | — |
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
Data sourced from ClinicalTrials.gov (NCT02875366) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.