Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation (DISCOVER)
27. srpna 2015 aktualizováno: Vertex Pharmaceuticals Incorporated
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
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.
Přehled studie
Detailní popis
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.
Typ studie
Intervenční
Zápis (Aktuální)
140
Fáze
- Fáze 2
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Alabama
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Birmingham, Alabama, Spojené státy, 35294
- University of Alabama
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Alaska
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Anchorage, Alaska, Spojené státy, 99508
- Providence Medical Center
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California
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Oakland, California, Spojené státy, 94611
- Kaiser Permanente Medical Care Program
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Connecticut
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Hartford, Connecticut, Spojené státy, 06106
- Connecticut Children's Medical Center
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Florida
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Miami, Florida, Spojené státy, 33136
- University of Miami Miller School of Medicine
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Orlando, Florida, Spojené státy, 32801
- Nemours Children's Clinic
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Idaho
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Boise, Idaho, Spojené státy, 83712
- St. Luke's CF Clinic
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Illinois
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Chicago, Illinois, Spojené státy, 60637
- University of Chicago
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Indiana
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Indianapolis, Indiana, Spojené státy, 46202
- Riley Hospital for Children
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Maine
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Portland, Maine, Spojené státy, 04102
- Maine Medical Center
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Massachusetts
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Boston, Massachusetts, Spojené státy, 02114
- Massachusetts General Hospital
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Worcester, Massachusetts, Spojené státy, 01655
- University of Massachussetts Medical School
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Michigan
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Grand Rapids, Michigan, Spojené státy, 49503
- Helen DeVos Children's Hospital; Spectrum Health Hospitals
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Missouri
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Kansas City, Missouri, Spojené státy, 64108
- The Children's Mercy Hospital
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New Hampshire
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Lebanon, New Hampshire, Spojené státy, 03756
- Dartmouth-Hitchcock Medical Center
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New Jersey
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Long Branch, New Jersey, Spojené státy, 07740
- Monmouth Medical Center
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Morristown, New Jersey, Spojené státy, 07962
- Morristown Memorial Hospital
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New York
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Albany, New York, Spojené státy, 12208
- Albany Medical College
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Buffalo, New York, Spojené státy, 14222
- Women and Children's Hospital of Buffalo
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Hawthorne, New York, Spojené státy, 10532
- New York Medical College
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New York, New York, Spojené státy, 10032
- Columbia University Medical Center
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New York City, New York, Spojené státy, 10003
- The CF Center, Beth Israel Medical Center
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Ohio
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Akron, Ohio, Spojené státy, 44308
- Akron Children's Hospital
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Cincinnati, Ohio, Spojené státy, 45229
- Cincinnati Children's Hospital
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Toledo, Ohio, Spojené státy, 43606
- Toldedo Children's Hospital
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Oklahoma
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Oklahoma City, Oklahoma, Spojené státy, 73104
- University of Oklahoma Health Sciences Center
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Pennsylvania
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Hershey, Pennsylvania, Spojené státy, 17033
- Hershey Medical Center
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Philadelphia, Pennsylvania, Spojené státy, 19134
- St. Christopher's Hospital for Children
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South Carolina
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Charleston, South Carolina, Spojené státy, 29425
- Medical University of South Carolina
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Tennessee
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Memphis, Tennessee, Spojené státy, 38103
- University of Tennessee
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Texas
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Fort Worth, Texas, Spojené státy, 76104
- Cook Children's Medical Center
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Utah
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Salt Lake City, Utah, Spojené státy, 84132
- Univeristy of Utah
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Vermont
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Colchester, Vermont, Spojené státy, 05446
- Vermont Lung Center at the University of Vermont
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Virginia
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Richmond, Virginia, Spojené státy, 23298
- Medical College of Virginia
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
12 let a starší (Dítě, Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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)
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Komparátor placeba: 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).
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Tableta
Tablet
Ostatní jména:
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Experimentální: 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).
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Tablet
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16
Časové okno: Part A baseline through Week 16
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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.
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Part A baseline through Week 16
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16
Časové okno: Part A baseline through Week 16
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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.
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Part A baseline through Week 16
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Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16
Časové okno: Part A baseline through Week 16
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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.
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Part A baseline through Week 16
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Part A : Rate of Change From Baseline in Weight Through Week 16
Časové okno: Part A baseline through Week 16
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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.
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Part A baseline through Week 16
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Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64
Časové okno: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
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ppFEV1 is defined in Outcome Measure 1.
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Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
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Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64
Časové okno: Part A baseline through Week 64
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ppFEV1 is defined in Outcome Measure 1.
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Part A baseline through Week 64
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Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64
Časové okno: Part B baseline through Week 64
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ppFEV1 is defined in Outcome Measure 1.
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Part B baseline through Week 64
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Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64
Časové okno: 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.
|
Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
|
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Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64
Časové okno: 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.
|
Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
|
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Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64
Časové okno: 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.
|
Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
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Part B : Number of Participants With Pulmonary Exacerbations
Časové okno: Part B baseline through Week 64
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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.
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Part B baseline through Week 64
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Part B : Number of Pulmonary Exacerbation Events
Časové okno: 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.
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Part B baseline through Week 64
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Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year
Časové okno: 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.
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Part B baseline through Week 64
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Patrick A Flume, MD, Medical University of South Carolina
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Užitečné odkazy
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. září 2009
Primární dokončení (Aktuální)
1. července 2010
Dokončení studie (Aktuální)
1. května 2013
Termíny zápisu do studia
První předloženo
4. srpna 2009
První předloženo, které splnilo kritéria kontroly kvality
5. srpna 2009
První zveřejněno (Odhad)
6. srpna 2009
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
11. září 2015
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
27. srpna 2015
Naposledy ověřeno
1. srpna 2015
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Nemoci trávicího systému
- Patologické procesy
- Nemoci dýchacích cest
- Plicní onemocnění
- Kojenec, novorozenec, nemoci
- Genetické choroby, vrozené
- Onemocnění slinivky břišní
- Fibróza
- Cystická fibróza
- Molekulární mechanismy farmakologického působení
- Membránové transportní modulátory
- Agonisté chloridového kanálu
- Ivacaftor
Další identifikační čísla studie
- VX08-770-104
- 2009-010261-23 (Číslo EudraCT)
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .