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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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ClinicalTrials.gov Identifier: NCT02875366
Recruitment Status : Completed
First Posted : August 23, 2016
Results First Posted : June 17, 2019
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: LUM/IVA Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
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
Actual Study Start Date : September 2016
Actual Primary Completion Date : September 2017
Actual Study Completion Date : October 2017


Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo matched to LUM/IVA fixed-dose combination tablet orally every 12 hours (q12h) for 24 weeks.
Drug: Placebo
Experimental: LUM/IVA
LUM 400 milligram (mg)/IVA 250 mg fixed-dose combination tablet orally q12h for 24 weeks.
Drug: LUM/IVA
Other Name: Lumacaftor/Ivacaftor




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Relative (Percent) Change From Baseline in Exercise Duration During CPET at Week 24 [ Time Frame: Baseline, 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.

  2. Absolute Change From Baseline in Exercise Duration During CPET at Week 24 [ Time Frame: Baseline, 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.

  3. Absolute Change From Baseline in VO2max During CPET at Week 24 [ Time Frame: Baseline, Week 24 ]
    CPET was used to assess change in exercise tolerance, as measured by VO2max.

  4. Absolute Change From Baseline in Oxygen Consumption (VO2) at Anaerobic Threshold at Week 24 [ Time Frame: Baseline, Week 24 ]
    Anaerobic threshold was defined as the exercise intensity at which lactate starts to accumulate.

  5. Relative (Percent) Change From Baseline in VO2 at Anaerobic Threshold at Week 24 [ Time Frame: Baseline, Week 24 ]
    Anaerobic threshold was defined as the exercise intensity at which lactate starts to accumulate.

  6. Absolute Change From Baseline in Functional VO2 Gain at Week 24 [ Time Frame: Baseline, Week 24 ]
  7. Relative (Percent) Change From Baseline in Functional VO2 Gain at Week 24 [ Time Frame: Baseline, Week 24 ]
  8. Absolute Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24 [ Time Frame: Baseline, Week 24 ]
  9. Relative (Percent) Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24 [ Time Frame: Baseline, Week 24 ]
  10. Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 [ Time Frame: Baseline, Week 24 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  11. Relative (Percent) Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 [ Time Frame: Baseline, Week 24 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  12. Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 [ Time Frame: Baseline, Week 24 ]
    BMI was defined as weight in kilograms (kg) divided by height in square meter (m^2).

  13. Relative (Percent) Change From Baseline in BMI at Week 24 [ Time Frame: Baseline, Week 24 ]
    BMI was defined as weight in kg divided by height in m^2.

  14. Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24 [ Time Frame: Baseline, 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.

  15. Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) [ Time Frame: Baseline, Week 24 ]
    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.

  16. Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores [ Time Frame: Baseline, Week 24 ]
    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.

  17. Absolute Change From Baseline in Daily Physical Activity Counts as Determined by Actigraphy at Week 24 [ Time Frame: Baseline, Week 24 ]
    Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily physical activity counts.

  18. Relative (Percent) Change From Baseline in Physical Activity as Determined by Actigraphy at Week 24 [ Time Frame: Baseline, Week 24 ]
    Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily physical activities.

  19. Absolute Change From Baseline in Duration of Sleep Time at Week 24 [ Time Frame: Baseline, Week 24 ]
    Participants were provided with a wrist-worn actigraphy device which continuously collected data about sleep duration and quality.

  20. Relative (Percent) Change From Baseline in Duration of Sleep Time at Week 24 [ Time Frame: Baseline, Week 24 ]
    Participants were provided with a wrist-worn actigraphy device which continuously collected data about sleep duration and quality.

  21. Absolute Change From Baseline in Time Above Sedentary Duration at Week 24 [ Time Frame: Baseline, Week 24 ]
    Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily activities and sleep duration and quality.

  22. Relative (Percent) Change From Baseline in Time Above Sedentary Duration at Week 24 [ Time Frame: Baseline, Week 24 ]
    Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily activities and sleep duration and quality.

  23. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Week 28 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02875366


Locations
Layout table for location information
Australia, Victoria
Melbourne, Victoria, Australia
Parkville, Victoria, Australia
Australia
Adelaide, Australia
Camperdown, Australia
Clayton, Australia
Nedlands, Australia
New Lambton Heights, Australia
Randwick, Australia
South Brisbane, Australia
Subiaco, Australia
Westmead, Australia
United Kingdom
Edinburgh, United Kingdom
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol  [PDF] January 15, 2016
Statistical Analysis Plan  [PDF] May 17, 2017


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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT02875366    
Other Study ID Numbers: VX15-809-112
2016‐000066‐34 ( EudraCT Number )
First Posted: August 23, 2016    Key Record Dates
Results First Posted: June 17, 2019
Last Update Posted: June 17, 2019
Last Verified: March 2019
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action