Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation (DISCOVER)
The purpose of this study was to evaluate the safety and efficacy of ivacaftor in patients with cystic fibrosis who were aged 12 years or older and were homozygous for the F508del-CFTR mutation. Ivacaftor is a potent and selective cystic fibrosis transmembrane conductance regulator (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.
|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|
- Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 16 [ Time Frame: baseline through 16 weeks ] [ Designated as safety issue: No ]Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
- Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score Through Week 16 (Respiratory Domain Score, Pooled) [ Time Frame: baseline through 16 weeks ] [ Designated as safety issue: No ]The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID).
- Absolute Change From Baseline in Sweat Chloride Concentration Through Week 16 [ Time Frame: baseline through 16 weeks ] [ 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.
- Rate of Change From Baseline in Weight Through Week 16 [ Time Frame: baseline to 16 weeks ] [ 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.
|Study Start Date:||September 2009|
|Estimated Study Completion Date:||June 2013|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Subjects in Part A who received placebo every 12 hours (q12h) for 16 weeks.
Tablets given orally q12h for 16 weeks
Experimental: 150 mg Ivacaftor q12h
Subjects in Part A who received 150 mg of ivacaftor q12h for 16 weeks.
150-mg tablets given orally q12h for 16 weeks
Other Name: VX-770
This study investigated the effects of ivacaftor in subjects with cystic fibrosis (CF) ≥ 12 years of age with an forced expiratory volume in 1 second (FEV1) ≥ 40% predicted. This study was conducted in 2 parts. This posting describes Part A only.
- Part A of this study was a randomized, double-blind, placebo-controlled, parallel-group evaluation of subjects with CF who were aged 12 years or older and were homozygous for the F508del-CFTR mutation. At 34 centers in the US, 140 subjects were enrolled and randomized to receive either 150 mg ivacaftor q12h (112 subjects) or placebo (28 subjects) for 16 weeks.
- Part B of this study was an open-label extension of Part A, enrolling subjects who completed Part A, and explored the safety and efficacy of ivacaftor over long-term treatment in subjects with CF aged 12 years or older who were homozygous for the F508del-CFTR mutation.
Show 34 Study Locations
|Principal Investigator:||Patrick A Flume, MD||Medical University of South Carolina|