Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation (DISCOVER)

This study has been terminated.
(Following review of results obtained from a pre-specified 6-month analysis of Part B data the study was terminated on the basis of futility.)
Sponsor:
Collaborator:
Cystic Fibrosis Foundation Therapeutics
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT00953706
First received: August 4, 2009
Last updated: July 29, 2015
Last verified: July 2015
  Purpose

The purpose of this study was to evaluate the safety and efficacy of ivacaftor in participants with cystic fibrosis (CF) who were aged 12 years or older and were homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. Ivacaftor is a potent and selective CFTR potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. Potentiators are pharmacological agents that increase the chloride ion transport properties of the channel in the presence of cyclic adenosine monophosphate (AMP)-dependent protein kinase A (PKA) activation.


Condition Intervention Phase
Cystic Fibrosis
Drug: Ivacaftor
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of VX-770 in Subjects Aged 12 Years and Older With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16 [ Time Frame: Part A baseline through Week 16 ] [ Designated as safety issue: No ]
    Spirometry (as measured by ppFEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Knudson method.


Secondary Outcome Measures:
  • Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16 [ Time Frame: Part A baseline through Week 16 ] [ Designated as safety issue: No ]
    The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; Higher scores indicating fewer symptoms and better health-related quality of life.

  • Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16 [ Time Frame: Part A baseline through Week 16 ] [ Designated as safety issue: No ]
    The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.

  • Part A : Rate of Change From Baseline in Weight Through Week 16 [ Time Frame: Part A baseline through Week 16 ] [ Designated as safety issue: No ]
    As malnutrition is common in participants with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.

  • Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64 [ Time Frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64 ] [ Designated as safety issue: No ]
    ppFEV1 is defined in Outcome Measure 1.

  • Part B : Rate of Decline From Part A Baseline in ppFEV1 Through Week 64 [ Time Frame: Part A baseline through Week 64 ] [ Designated as safety issue: No ]
    ppFEV1 is defined in Outcome Measure 1.

  • Part B : Rate of Decline From Part B Baseline in ppFEV1 Through Week 64 [ Time Frame: Part B baseline through Week 64 ] [ Designated as safety issue: No ]
    ppFEV1 is defined in Outcome Measure 1.

  • Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64 [ Time Frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64 ] [ Designated as safety issue: No ]
    The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; Higher scores indicating fewer symptoms and better health-related quality of life.

  • Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64 [ Time Frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64 ] [ Designated as safety issue: No ]
    The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.

  • Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64 [ Time Frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64 ] [ Designated as safety issue: No ]
    As malnutrition is common in patients with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.

  • Part B : Number of Participants With Pulmonary Exacerbations [ Time Frame: Part B baseline through Week 64 ] [ Designated as safety issue: No ]
    Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.

  • Part B : Number of Pulmonary Exacerbation Events [ Time Frame: Part B baseline through Week 64 ] [ Designated as safety issue: No ]
    Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.

  • Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year [ Time Frame: Part B baseline through Week 64 ] [ Designated as safety issue: No ]
    Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.


Enrollment: 140
Study Start Date: September 2009
Study Completion Date: May 2013
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period), followed by ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Drug: Ivacaftor
Tablet
Other Name: VX-770
Drug: Placebo
Tablet
Experimental: Ivacaftor
Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period), followed by ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Drug: Ivacaftor
Tablet
Other Name: VX-770

Detailed Description:

This study investigated the effects of ivacaftor in participants with cystic fibrosis (CF) >=12 years of age with a forced expiratory volume in 1 second (FEV1) >=40 percent (%) predicted. This study was conducted in 2 parts.

  • Part A of this study was a randomized, double-blind, placebo-controlled, parallel-group evaluation of participants with CF who were aged 12 years or older and were homozygous for the F508del-CFTR mutation.
  • Part B of this study was an open-label extension of Part A, enrolling participants who completed Part A and met pre-specified endpoint criteria, and explored the safety and efficacy of ivacaftor over long-term treatment in participants with CF aged 12 years or older who were homozygous for the F508del-CFTR mutation.
  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of cystic fibrosis (CF) and homozygous for F508del-CFTR mutation
  • Forced expiratory volume in 1 second (FEV1) of at least 40% of predicted normal for age, gender, and height
  • Willing to use at least 2 highly effective birth control methods during the study
  • No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator
  • Able to understand and comply with protocol requirements, restrictions, and instructions and likely to complete the study as planned, as judged by the investigator

Exclusion Criteria:

  • History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject
  • Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1 of the study
  • History of alcohol, medication or illicit drug abuse within one year prior to Day 1
  • Abnormal liver function >=3 x the upper limit of normal
  • Abnormal renal function at Screening
  • History of solid organ or hematological transplantation
  • Pregnant or breast-feeding (for women)
  • Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to screening
  • Previous participation in a VX-809 study
  • Used inhaled hypertonic saline treatment
  • Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP3A4)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00953706

  Show 34 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Cystic Fibrosis Foundation Therapeutics
Investigators
Principal Investigator: Patrick A Flume, MD Medical University of South Carolina
  More Information

Additional Information:
No publications provided by Vertex Pharmaceuticals Incorporated

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT00953706     History of Changes
Other Study ID Numbers: VX08-770-104, 2009-010261-23
Study First Received: August 4, 2009
Results First Received: February 27, 2012
Last Updated: July 29, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Vertex Pharmaceuticals Incorporated:
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 03, 2015