NCT02875366CompletedPhase 4
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
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 70
- Primary Endpoint
- Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Placebo
Placebo Comparator
Placebo matched to LUM/IVA fixed-dose combination tablet orally every 12 hours (q12h) for 24 weeks.
Intervention: Placebo (Drug)
LUM/IVA
Experimental
LUM 400 milligram (mg)/IVA 250 mg fixed-dose combination tablet orally q12h for 24 weeks.
Intervention: LUM/IVA (Drug)
Outcomes
Primary Outcomes
Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24
Time Frame: Baseline, Week 24
CPET was used to assess change in exercise tolerance, as measured by VO2max.
Secondary Outcomes
- Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24(Baseline, Week 24)
- Relative (Percent) Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24(Baseline, Week 24)
- Relative (Percent) Change From Baseline in Functional VO2 Gain at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24(Baseline, Week 24)
- Relative (Percent) Change From Baseline in Duration of Sleep Time at Week 24(Baseline, Week 24)
- Relative (Percent) Change From Baseline in VO2 at Anaerobic Threshold at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in Functional VO2 Gain at Week 24(Baseline, Week 24)
- Relative (Percent) Change From Baseline in BMI at Week 24(Baseline, Week 24)
- Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8)(Baseline, Week 24)
- Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores(Baseline, Week 24)
- Relative (Percent) Change From Baseline in Exercise Duration During CPET at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in Exercise Duration During CPET at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in VO2max During CPET at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in Oxygen Consumption (VO2) at Anaerobic Threshold at Week 24(Baseline, Week 24)
- Relative (Percent) Change From Baseline in Physical Activity as Determined by Actigraphy at Week 24(Baseline, Week 24)
- Relative (Percent) Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in Body Mass Index (BMI) at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in Daily Physical Activity Counts as Determined by Actigraphy at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in Duration of Sleep Time at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in Time Above Sedentary Duration at Week 24(Baseline, Week 24)
- Relative (Percent) Change From Baseline in Time Above Sedentary Duration at Week 24(Baseline, Week 24)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Day 1 up to Week 28)
Investigators
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