Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation
- Registration Number
- NCT00953706
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 140
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo 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). Placebo Ivacaftor 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). Ivacaftor 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).
- Primary Outcome Measures
Name Time Method Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16 Part A baseline through Week 16 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
Name Time Method Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16 Part A baseline through Week 16 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 Part A baseline through Week 16 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 Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64 ppFEV1 is defined in Outcome Measure 1.
Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64 Part A baseline through Week 64 ppFEV1 is defined in Outcome Measure 1.
Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16 Part A baseline through Week 16 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 : Rate of Change From Part B Baseline in ppFEV1 Through Week 64 Part B baseline through Week 64 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 Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64 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 Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64 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 : Number of Participants With Pulmonary Exacerbations Part B baseline through Week 64 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 : Absolute Change From Part A and Part B Baseline in Weight Through Week 64 Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64 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 Pulmonary Exacerbation Events Part B baseline through Week 64 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 Part B baseline through Week 64 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.
Trial Locations
- Locations (34)
Maine Medical Center
🇺🇸Portland, Maine, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
University of Alabama
🇺🇸Birmingham, Alabama, United States
Kaiser Permanente Medical Care Program
🇺🇸Oakland, California, United States
Providence Medical Center
🇺🇸Anchorage, Alaska, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Nemours Children's Clinic
🇺🇸Orlando, Florida, United States
St. Luke's CF clinic
🇺🇸Boise, Idaho, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Massachussetts Medical School
🇺🇸Worcester, Massachusetts, United States
Helen DeVos Children's Hospital; Spectrum Health Hospitals
🇺🇸Grand Rapids, Michigan, United States
The Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Monmouth Medical Center
🇺🇸Long Branch, New Jersey, United States
Morristown Memorial Hospital
🇺🇸Morristown, New Jersey, United States
New York Medical College
🇺🇸Hawthorne, New York, United States
The CF Center, Beth Israel Medical Center
🇺🇸New York City, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Cincinnati Children's Hospital
🇺🇸Cincinnati, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
St. Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Tennessee
🇺🇸Memphis, Tennessee, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Vermont Lung Center at the University of Vermont
🇺🇸Colchester, Vermont, United States
Medical College of Virginia
🇺🇸Richmond, Virginia, United States
Univeristy of Utah
🇺🇸Salt Lake City, Utah, United States
Toldedo Children's Hospital
🇺🇸Toledo, Ohio, United States
Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Albany Medical College
🇺🇸Albany, New York, United States
Women and Children's Hospital of Buffalo
🇺🇸Buffalo, New York, United States