Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older With the G551D Mutation (STRIVE)
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of VX-770 in Subjects With Cystic Fibrosis and the G551D Mutation
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Fase
Fase
- Fase 3
Kontakter og lokationer
Studiesteder
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New South Wales
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Westmead, New South Wales, Australien, 2145
- The Children's Hospital Westmead
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Queensland
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Chermside, Queensland, Australien, 4032
- The Prince Charles Hospital
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Herston, Queensland, Australien, 4026
- Royal Children's Hospital Brisbane
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South Brisbane, Queensland, Australien, 4101
- Mater Adult Hospital
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Victoria
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Parkville, Victoria, Australien, 3052
- Royal Children's Hospital Melbourne
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Western Australia
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Nedlands, Western Australia, Australien, 6009
- Lung Institute of Western Australia
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Subiaco, Western Australia, Australien, 6008
- Princess Margaret Hospital for Children
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 3A7
- Queen Elizabeth Ii Health Sciences Centre
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Ontario
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Toronto, Ontario, Canada, M5B 1W8
- St. Michael's Hospital
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Toronto, Ontario, Canada, M5G 1X8
- CF Center, Hospital for Sick Children
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Quebec
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Montreal, Quebec, Canada, H3H 1P3
- Montreal Children's Hospital - MUHC
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London, Det Forenede Kongerige, SW3 6LR
- Imperial College London
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Northern Ireland
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Belfast, Northern Ireland, Det Forenede Kongerige, BT9 7AB
- Belfast City Hospital
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Alabama
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Birmingham, Alabama, Forenede Stater, 35233-1711
- University of Alabama
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California
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Oakland, California, Forenede Stater, 94611
- Kaiser Permanente Medical Care Program
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Palo Alto, California, Forenede Stater, 94304
- Cystic Fibrosis Research Office, Stanford University
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San Diego, California, Forenede Stater, 92123-5070
- Rady Children's Hospital
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Colorado
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Denver, Colorado, Forenede Stater, 80206
- National Jewish Medical and Research Center
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Georgia
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Atlanta, Georgia, Forenede Stater, 30322
- Emory Cystic Fibrosis Center
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Idaho
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Boise, Idaho, Forenede Stater, 83712
- St. Luke's CF Clinic
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Illinois
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Chicago, Illinois, Forenede Stater, 60614
- Children's Memorial Hospital
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Indiana
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Indianapolis, Indiana, Forenede Stater, 46202
- Indiana University
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Iowa
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Iowa City, Iowa, Forenede Stater, 52242
- University of Iowa
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Maryland
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Baltimore, Maryland, Forenede Stater, 21205
- Johns Hopkins University
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, Forenede Stater, 02115
- Children's Hospital Boston
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109
- University of Michigan
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Minnesota
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Minneapolis, Minnesota, Forenede Stater, 55455
- Pulmonary, Allergy & Critical Care Medicine, University of Minnesota
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Missouri
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Kansas City, Missouri, Forenede Stater, 64108
- The Children's Mercy Hospital
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St. Louis, Missouri, Forenede Stater, 63110
- Washington University
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Nebraska
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Omaha, Nebraska, Forenede Stater, 68198-5300
- Adult Pulmonary/ CF, University of Nebraska Medical Center
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New Jersey
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Long Branch, New Jersey, Forenede Stater, 07740
- Monmouth Medical Center
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New York
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Buffalo, New York, Forenede Stater, 14222
- Women and Children's Hospital of Buffalo
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New Hyde Park, New York, Forenede Stater, 11042
- Long Island Jewish Medical Center
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Syracuse, New York, Forenede Stater, 13210
- SUNY Upstate Medical University
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North Carolina
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Chapel Hill, North Carolina, Forenede Stater, 27599
- University of North Carolina at Chapel Hill
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Ohio
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Cincinnati, Ohio, Forenede Stater, 45229
- Cincinnati Children's Hospital Medical Center
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Cleveland, Ohio, Forenede Stater, 44106
- Pediatric & Pulmonary Division, Rainbow Babies/Case Western
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Columbus, Ohio, Forenede Stater, 43205
- Nationwide Children's Hospital
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Toledo, Ohio, Forenede Stater, 43606
- Toledo Children's Hospital
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Oregon
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Portland, Oregon, Forenede Stater, 97239-3098
- Oregon Health & Sciences University
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Pennsylvania
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Hershey, Pennsylvania, Forenede Stater, 17033
- Hershey Medical Center
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Philadelphia, Pennsylvania, Forenede Stater, 19104
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Forenede Stater, 15224
- Children's Hospital of Pittsburgh of UPMC
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Tennessee
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Knoxville, Tennessee, Forenede Stater, 37916
- East Tennessee Children's Hospital
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Nashville, Tennessee, Forenede Stater, 37232-5735
- Vanderbilt University Medical Center
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Utah
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Salt Lake City, Utah, Forenede Stater, 84132
- University of Utah
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Virginia
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Charlottesville, Virginia, Forenede Stater, 22908
- University of Virginia
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Washington
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Seattle, Washington, Forenede Stater, 98105
- Seattle Children's Hospital
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Seattle, Washington, Forenede Stater, 98195-6522
- Division of Pulmonary and CCM, University of Washington
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West Virginia
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Morgantown, West Virginia, Forenede Stater, 26506
- West Virginia University
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Wisconsin
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Milwaukee, Wisconsin, Forenede Stater, 53226
- Medical College of Wisconsin
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Paris, Frankrig, 75014
- Hôpital Cochin
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Paris, Frankrig, 75015
- Hopital Necker
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Roscoff, Frankrig, 29684
- Centre de Perharidy
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Cork, Irland
- Cork University Hospital
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Dublin, Irland, 9
- Beaumont Hospital
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Dublin, Irland, 4
- St. Vincent'S University Hospital
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Dublin, Irland, 12
- Our Lady's Children's Hospital
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Dublin, Irland, 24
- The National Children's Hospital
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Prague, Tjekkiet, 15006
- FN Motol
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Erlangen, Tyskland, 91054
- Kinder- und Jugendklinik Universitätsklinikum Erlangen
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Jena, Tyskland, 07740
- Mukoviszidose-Zentrum am Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Kinder- und Jugendmedizin
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Munich, Tyskland, 80337
- Klinikum der LMU München, Dr. von Haunersches Kinderspital (CHA)
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Wurzburg, Tyskland, 97080
- Universitäts-Kinderklinik Würzburg
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- 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
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 ≥ 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)
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
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Placebo komparator: Placebo
Forsøgspersoner, der fik placebo hver 12. time (q12h) i op til 48 uger.
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Tablet givet oralt hver 12. time i op til 48 uger
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Eksperimentel: 150 mg Ivacaftor q12h
Forsøgspersoner, der fik 150 mg ivacaftor hver 12. time i op til 48 uger.
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150-mg tablets given orally q12h for up to 48 weeks
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Absolute Mean Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
Tidsramme: baseline through 24 weeks
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Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
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baseline through 24 weeks
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Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Absolut ændring fra baseline i svedkloridkoncentration gennem uge 24 og uge 48
Tidsramme: baseline gennem 24 uger og 48 uger
|
Svedklorid-testen (kvantitativ pilocarpiniontoforese) er et standard diagnostisk værktøj til cystisk fibrose (CF), der tjener som en indikator for cystisk fibrose transmembrankonduktansregulator (CFTR) aktivitet.
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baseline gennem 24 uger og 48 uger
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Absolut ændring fra baseline i vægt i uge 24 og uge 48
Tidsramme: baseline til 24 uger og 48 uger
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Da underernæring er almindelig hos patienter med cystisk fibrose (CF) på grund af øget energiforbrug på grund af lungesygdom og fedtmalabsorption, er kropsvægt et vigtigt klinisk mål for ernæringsstatus.
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baseline til 24 uger og 48 uger
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Absolute Mean Change From Baseline in Percent Predicted FEV1 Through Week 48
Tidsramme: 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.
|
baseline through 48 weeks
|
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Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score Through Week 24 and Week 48 (Respiratory Domain Score, Pooled)
Tidsramme: 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).
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baseline through 24 weeks and 48 weeks
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Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48
Tidsramme: baseline through 24 weeks and 48 weeks
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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.
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baseline through 24 weeks and 48 weeks
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Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Samarbejdspartnere
Samarbejdspartnere
Efterforskere
Efterforskere
- Ledende efterforsker: Bonnie W. Ramsey, MD, Children's Hospital and Regional Medical Center, Seattle, Washington, USA
- Ledende efterforsker: Stuart Elborn, MD, Respiratory Medicine Group, Queen's University of Belfast, Belfast, Northern Ireland, UK
Publikationer og nyttige links
Generelle publikationer
- Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Drevinek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordonez C, Elborn JS; VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011 Nov 3;365(18):1663-72. doi: 10.1056/NEJMoa1105185.
- Flume PA, Wainwright CE, Elizabeth Tullis D, Rodriguez S, Niknian M, Higgins M, Davies JC, Wagener JS. Recovery of lung function following a pulmonary exacerbation in patients with cystic fibrosis and the G551D-CFTR mutation treated with ivacaftor. J Cyst Fibros. 2018 Jan;17(1):83-88. doi: 10.1016/j.jcf.2017.06.002. Epub 2017 Jun 24.
- Solem CT, Vera-Llonch M, Liu S, Botteman M, Castiglione B. Impact of pulmonary exacerbations and lung function on generic health-related quality of life in patients with cystic fibrosis. Health Qual Life Outcomes. 2016 Apr 21;14:63. doi: 10.1186/s12955-016-0465-z.
- Quittner A, Suthoff E, Rendas-Baum R, Bayliss MS, Sermet-Gaudelus I, Castiglione B, Vera-Llonch M. Effect of ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation: patient-reported outcomes in the STRIVE randomized, controlled trial. Health Qual Life Outcomes. 2015 Jul 2;13:93. doi: 10.1186/s12955-015-0293-6.
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Faktiske)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- VX08-770-102
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