Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older With the G551D Mutation
- Registration Number
- NCT00909532
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
The purpose of this study was to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis aged 12 years and older who have the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. 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 AMP-dependent protein kinase A (PKA) activation.
- Detailed Description
This was a phase 3 study in subjects with cystic fibrosis (CF) age 12 years and older who have a G551D-CFTR mutation and percent predicted forced expiratory volumn in 1 second (FEV1) between 40% and 90%.
Based on in vitro studies and pharmacologic, pharmacokinetic (PK), and safety profiles, ivacaftor was selected for clinical development as a possible treatment for patients with CF. Patients with the G551D mutation were the targeted population for this study because ivacaftor is a potentiator of the gating function of the CFTR protein, and the most prevalent mutation with a gating defect in CF is the G551D mutation.
This study was designed to further evaluate the efficacy of ivacaftor in subjects with CF who have a G551D-CFTR gene mutation and to evaluate safety in this population over a longer period than previously studied.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 167
- Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele
- Forced expiratory volume in 1 second (FEV1) of 40% to 90% (inclusive) of predicted normal for age, gender, and height at Screening.
- No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator
- Willing to use highly effective birth control methods during the study
- 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 ≥ 3x the upper limit of normal
- Abnormal renal function at Screening
- History of solid organ or hematological transplantation
- Pregnant, planning a pregnancy, breast-feeding, or unwilling to follow contraception requirements
- Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to Screening
- Use of inhaled hypertonic saline treatment
- Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Subjects who received placebo every 12 hours (q12h) for up to 48 weeks. 150 mg Ivacaftor q12h Ivacaftor Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.
- Primary Outcome Measures
Name Time Method Absolute Mean Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24 baseline through 24 weeks Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
- Secondary Outcome Measures
Name Time Method Absolute Mean Change From Baseline in Percent Predicted FEV1 Through Week 48 baseline through 48 weeks 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 24 and Week 48 (Respiratory Domain Score, Pooled) baseline through 24 weeks and 48 weeks 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 24 and Week 48 baseline through 24 weeks and 48 weeks 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.
Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48 baseline through 24 weeks and 48 weeks Pulmonary exacerbation was defined as a change in antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of signs/symptoms such as change in sputum; new or increased hemoptysis; increased cough or dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees C; anorexia or weight loss; sinus pain/tenderness and discharge; change in physical examination of the chest; decreased pulmonary function by 10%; and radiographic changes indicative of pulmonary infection.
Absolute Change From Baseline in Weight at Week 24 and Week 48 baseline to 24 weeks and 48 weeks 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.
Trial Locations
- Locations (65)
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Royal Children's Hospital Brisbane
🇦🇺Herston, Queensland, Australia
Rady Children's Hospital
🇺🇸San Diego, California, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Princess Margaret Hospital for Children
🇦🇺Subiaco, Western Australia, Australia
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
FN Motol
🇨🇿Prague, Czech Republic
West Virginia University
🇺🇸Morgantown, West Virginia, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Queen Elizabeth II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
National Jewish Medical and Research Center
🇺🇸Denver, Colorado, United States
University of Alabama
🇺🇸Birmingham, Alabama, United States
Oregon Health & Sciences University
🇺🇸Portland, Oregon, United States
Pulmonary, Allergy & Critical Care Medicine, University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Adult Pulmonary/ CF, University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Kaiser Permanente Medical Care Program
🇺🇸Oakland, California, United States
Emory Cystic Fibrosis Center
🇺🇸Atlanta, Georgia, United States
Children's Memorial Hospital
🇺🇸Chicago, Illinois, United States
Washington University
🇺🇸St. Louis, Missouri, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
The Children's Hospital Westmead
🇦🇺Westmead, New South Wales, Australia
Royal Children's Hospital Melbourne
🇦🇺Parkville, Victoria, Australia
Women and Children's Hospital of Buffalo
🇺🇸Buffalo, New York, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
St. Luke's CF Clinic
🇺🇸Boise, Idaho, United States
Cystic Fibrosis Research Office, Stanford University
🇺🇸Palo Alto, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Hopital Necker
🇫🇷Paris, France
Pediatric & Pulmonary Division, Rainbow Babies/Case Western
🇺🇸Cleveland, Ohio, United States
Toledo Children's Hospital
🇺🇸Toledo, Ohio, United States
Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
East Tennessee Children's Hospital
🇺🇸Knoxville, Tennessee, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Division of Pulmonary and CCM, University of Washington
🇺🇸Seattle, Washington, United States
The Prince Charles Hospital
🇦🇺Chermside, Queensland, Australia
Mater Adult Hospital
🇦🇺South Brisbane, Queensland, Australia
Lung Institute of Western Australia
🇦🇺Nedlands, Western Australia, Australia
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Montreal Children's Hospital - MUHC
🇨🇦Montreal, Quebec, Canada
CF Center, Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Hopital Cochin
🇫🇷Paris, France
Kinder- und Jugendklinik Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
Centre de Perharidy
🇫🇷Roscoff, France
Mukoviszidose-Zentrum am Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Kinder- und Jugendmedizin
🇩🇪Jena, Germany
Universitäts-Kinderklinik Würzburg
🇩🇪Wurzburg, Germany
Klinikum der LMU München, Dr. von Haunersches Kinderspital (CHA)
🇩🇪Munich, Germany
Our Lady's Children's Hospital
🇮🇪Dublin, Ireland
The National Children's Hospital
🇮🇪Dublin, Ireland
Cork University Hospital
🇮🇪Cork, Ireland
St. Vincent's University Hospital
🇮🇪Dublin, Ireland
Beaumont Hospital
🇮🇪Dublin, Ireland
Belfast City Hospital
🇬🇧Belfast, Northern Ireland, United Kingdom
Imperial College London
🇬🇧London, United Kingdom
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
The Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Monmouth Medical Center
🇺🇸Long Branch, New Jersey, United States