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Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation (DISCOVER)

27. August 2015 aktualisiert von: 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.

Studienübersicht

Status

Beendet

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

140

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Vereinigte Staaten
    • Alabama
      • Birmingham, Alabama, Vereinigte Staaten, 35294
        • University of Alabama
    • Alaska
      • Anchorage, Alaska, Vereinigte Staaten, 99508
        • Providence Medical Center
    • California
      • Oakland, California, Vereinigte Staaten, 94611
        • Kaiser Permanente Medical Care Program
    • Connecticut
      • Hartford, Connecticut, Vereinigte Staaten, 06106
        • Connecticut Children's Medical Center
    • Florida
      • Miami, Florida, Vereinigte Staaten, 33136
        • University of Miami Miller School of Medicine
      • Orlando, Florida, Vereinigte Staaten, 32801
        • Nemours Children's Clinic
    • Idaho
      • Boise, Idaho, Vereinigte Staaten, 83712
        • St. Luke's CF Clinic
    • Illinois
      • Chicago, Illinois, Vereinigte Staaten, 60637
        • University of Chicago
    • Indiana
      • Indianapolis, Indiana, Vereinigte Staaten, 46202
        • Riley Hospital for Children
    • Maine
      • Portland, Maine, Vereinigte Staaten, 04102
        • Maine Medical Center
    • Massachusetts
      • Boston, Massachusetts, Vereinigte Staaten, 02114
        • Massachusetts General Hospital
      • Worcester, Massachusetts, Vereinigte Staaten, 01655
        • University of Massachussetts Medical School
    • Michigan
      • Grand Rapids, Michigan, Vereinigte Staaten, 49503
        • Helen DeVos Children's Hospital; Spectrum Health Hospitals
    • Missouri
      • Kansas City, Missouri, Vereinigte Staaten, 64108
        • The Children's Mercy Hospital
    • New Hampshire
      • Lebanon, New Hampshire, Vereinigte Staaten, 03756
        • Dartmouth-Hitchcock Medical Center
    • New Jersey
      • Long Branch, New Jersey, Vereinigte Staaten, 07740
        • Monmouth Medical Center
      • Morristown, New Jersey, Vereinigte Staaten, 07962
        • Morristown Memorial Hospital
    • New York
      • Albany, New York, Vereinigte Staaten, 12208
        • Albany Medical College
      • Buffalo, New York, Vereinigte Staaten, 14222
        • Women and Children's Hospital of Buffalo
      • Hawthorne, New York, Vereinigte Staaten, 10532
        • New York Medical College
      • New York, New York, Vereinigte Staaten, 10032
        • Columbia University Medical Center
      • New York City, New York, Vereinigte Staaten, 10003
        • The CF Center, Beth Israel Medical Center
    • Ohio
      • Akron, Ohio, Vereinigte Staaten, 44308
        • Akron Children's Hospital
      • Cincinnati, Ohio, Vereinigte Staaten, 45229
        • Cincinnati Children's Hospital
      • Toledo, Ohio, Vereinigte Staaten, 43606
        • Toldedo Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, Vereinigte Staaten, 73104
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Hershey, Pennsylvania, Vereinigte Staaten, 17033
        • Hershey Medical Center
      • Philadelphia, Pennsylvania, Vereinigte Staaten, 19134
        • St. Christopher's Hospital for Children
    • South Carolina
      • Charleston, South Carolina, Vereinigte Staaten, 29425
        • Medical University of South Carolina
    • Tennessee
      • Memphis, Tennessee, Vereinigte Staaten, 38103
        • University of Tennessee
    • Texas
      • Fort Worth, Texas, Vereinigte Staaten, 76104
        • Cook Children's Medical Center
    • Utah
      • Salt Lake City, Utah, Vereinigte Staaten, 84132
        • Univeristy of Utah
    • Vermont
      • Colchester, Vermont, Vereinigte Staaten, 05446
        • Vermont Lung Center at the University of Vermont
    • Virginia
      • Richmond, Virginia, Vereinigte Staaten, 23298
        • Medical College of Virginia

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

12 Jahre und älter (Kind, Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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)

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Vervierfachen

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Placebo-Komparator: 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).
Arzneimittel: Placebo
Tablette
Arzneimittel: Ivacaftor
Tablet
Andere Namen:
  • VX-770
Experimental: 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).
Arzneimittel: Ivacaftor
Tablet
Andere Namen:
  • VX-770

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16
Zeitfenster: 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.
Part A baseline through Week 16

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16
Zeitfenster: 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 A baseline through Week 16
Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16
Zeitfenster: 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 baseline through Week 16
Part A : Rate of Change From Baseline in Weight Through Week 16
Zeitfenster: 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 A baseline through Week 16
Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64
Zeitfenster: 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.
Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64
Zeitfenster: Part A baseline through Week 64
ppFEV1 is defined in Outcome Measure 1.
Part A baseline through Week 64
Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64
Zeitfenster: Part B baseline through Week 64
ppFEV1 is defined in Outcome Measure 1.
Part B baseline through Week 64
Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64
Zeitfenster: 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
Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64
Zeitfenster: 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
Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64
Zeitfenster: 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
Part B : Number of Participants With Pulmonary Exacerbations
Zeitfenster: 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 baseline through Week 64
Part B : Number of Pulmonary Exacerbation Events
Zeitfenster: 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 baseline through Week 64
Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year
Zeitfenster: 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 baseline through Week 64

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Vertex Pharmaceuticals Incorporated

Mitarbeiter

Cystic Fibrosis Foundation

Ermittler

  • Hauptermittler: Patrick A Flume, MD, Medical University of South Carolina

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Nützliche Links

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. September 2009

Primärer Abschluss (Tatsächlich)

1. Juli 2010

Studienabschluss (Tatsächlich)

1. Mai 2013

Studienanmeldedaten

Zuerst eingereicht

4. August 2009

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

5. August 2009

Zuerst gepostet (Schätzen)

6. August 2009

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Schätzen)

11. September 2015

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

27. August 2015

Zuletzt verifiziert

1. August 2015

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • VX08-770-104
  • 2009-010261-23 (EudraCT-Nummer)

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