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- Registre américain des essais cliniques
- Essai clinique NCT00953706
Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation (DISCOVER)
27 août 2015 mis à jour par: 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.
Aperçu de l'étude
Statut
Résilié
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Interventionnel
Inscription (Réel)
140
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Alabama
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Birmingham, Alabama, États-Unis, 35294
- University of Alabama
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Alaska
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Anchorage, Alaska, États-Unis, 99508
- Providence Medical Center
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California
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Oakland, California, États-Unis, 94611
- Kaiser Permanente Medical Care Program
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Connecticut
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Hartford, Connecticut, États-Unis, 06106
- Connecticut Children's Medical Center
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Florida
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Miami, Florida, États-Unis, 33136
- University of Miami Miller School of Medicine
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Orlando, Florida, États-Unis, 32801
- Nemours Children's Clinic
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Idaho
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Boise, Idaho, États-Unis, 83712
- St. Luke's CF Clinic
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Illinois
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Chicago, Illinois, États-Unis, 60637
- University of Chicago
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Indiana
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Indianapolis, Indiana, États-Unis, 46202
- Riley Hospital for Children
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Maine
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Portland, Maine, États-Unis, 04102
- Maine Medical Center
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Massachusetts
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Boston, Massachusetts, États-Unis, 02114
- Massachusetts General Hospital
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Worcester, Massachusetts, États-Unis, 01655
- University of Massachussetts Medical School
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Michigan
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Grand Rapids, Michigan, États-Unis, 49503
- Helen DeVos Children's Hospital; Spectrum Health Hospitals
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Missouri
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Kansas City, Missouri, États-Unis, 64108
- The Children's Mercy Hospital
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New Hampshire
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Lebanon, New Hampshire, États-Unis, 03756
- Dartmouth-Hitchcock Medical Center
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New Jersey
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Long Branch, New Jersey, États-Unis, 07740
- Monmouth Medical Center
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Morristown, New Jersey, États-Unis, 07962
- Morristown Memorial Hospital
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New York
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Albany, New York, États-Unis, 12208
- Albany Medical College
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Buffalo, New York, États-Unis, 14222
- Women and Children's Hospital of Buffalo
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Hawthorne, New York, États-Unis, 10532
- New York Medical College
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New York, New York, États-Unis, 10032
- Columbia University Medical Center
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New York City, New York, États-Unis, 10003
- The CF Center, Beth Israel Medical Center
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Ohio
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Akron, Ohio, États-Unis, 44308
- Akron Children's Hospital
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Cincinnati, Ohio, États-Unis, 45229
- Cincinnati Children's Hospital
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Toledo, Ohio, États-Unis, 43606
- Toldedo Children's Hospital
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Oklahoma
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Oklahoma City, Oklahoma, États-Unis, 73104
- University of Oklahoma Health Sciences Center
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Pennsylvania
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Hershey, Pennsylvania, États-Unis, 17033
- Hershey Medical Center
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Philadelphia, Pennsylvania, États-Unis, 19134
- St. Christopher's Hospital for Children
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South Carolina
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Charleston, South Carolina, États-Unis, 29425
- Medical University of South Carolina
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Tennessee
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Memphis, Tennessee, États-Unis, 38103
- University of Tennessee
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Texas
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Fort Worth, Texas, États-Unis, 76104
- Cook Children's Medical Center
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Utah
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Salt Lake City, Utah, États-Unis, 84132
- Univeristy of Utah
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Vermont
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Colchester, Vermont, États-Unis, 05446
- Vermont Lung Center at The University of Vermont
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Virginia
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Richmond, Virginia, États-Unis, 23298
- Medical College of Virginia
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
12 ans et plus (Enfant, Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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)
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Comparateur 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).
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Tablette
Tablet
Autres noms:
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Expérimental: 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
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16
Délai: 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.
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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
Délai: 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.
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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
Délai: 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
Délai: 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
Délai: 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
Délai: Part B baseline through Week 64
|
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
Délai: 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.
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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 : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64
Délai: 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
Délai: 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.
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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 : Number of Participants With Pulmonary Exacerbations
Délai: 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
Délai: 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 Per Participant Per Year
Délai: 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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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Patrick A Flume, MD, Medical University of South Carolina
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Liens utiles
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 septembre 2009
Achèvement primaire (Réel)
1 juillet 2010
Achèvement de l'étude (Réel)
1 mai 2013
Dates d'inscription aux études
Première soumission
4 août 2009
Première soumission répondant aux critères de contrôle qualité
5 août 2009
Première publication (Estimation)
6 août 2009
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
11 septembre 2015
Dernière mise à jour soumise répondant aux critères de contrôle qualité
27 août 2015
Dernière vérification
1 août 2015
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies du système digestif
- Processus pathologiques
- Maladies des voies respiratoires
- Maladies pulmonaires
- Nourrisson, nouveau-né, maladies
- Maladies génétiques, innées
- Maladies pancréatiques
- Fibrose
- Fibrose kystique
- Mécanismes moléculaires de l'action pharmacologique
- Modulateurs de transport membranaire
- Agonistes des canaux chlorure
- Ivacaftor
Autres numéros d'identification d'étude
- VX08-770-104
- 2009-010261-23 (Numéro EudraCT)
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
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