Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation (DISCOVER)
2015년 8월 27일 업데이트: 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.
연구 개요
상세 설명
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.
연구 유형
중재적
등록 (실제)
140
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Alabama
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Birmingham, Alabama, 미국, 35294
- University Of Alabama
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Alaska
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Anchorage, Alaska, 미국, 99508
- Providence Medical Center
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California
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Oakland, California, 미국, 94611
- Kaiser Permanente Medical Care Program
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Connecticut
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Hartford, Connecticut, 미국, 06106
- Connecticut Children's Medical Center
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Florida
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Miami, Florida, 미국, 33136
- University of Miami Miller School of Medicine
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Orlando, Florida, 미국, 32801
- Nemours Children's Clinic
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Idaho
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Boise, Idaho, 미국, 83712
- St. Luke's CF Clinic
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Illinois
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Chicago, Illinois, 미국, 60637
- University of Chicago
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Indiana
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Indianapolis, Indiana, 미국, 46202
- Riley Hospital for Children
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Maine
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Portland, Maine, 미국, 04102
- Maine Medical Center
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Massachusetts
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Boston, Massachusetts, 미국, 02114
- Massachusetts General Hospital
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Worcester, Massachusetts, 미국, 01655
- University of Massachussetts Medical School
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Michigan
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Grand Rapids, Michigan, 미국, 49503
- Helen DeVos Children's Hospital; Spectrum Health Hospitals
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Missouri
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Kansas City, Missouri, 미국, 64108
- The Children's Mercy Hospital
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New Hampshire
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Lebanon, New Hampshire, 미국, 03756
- Dartmouth-Hitchcock Medical Center
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New Jersey
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Long Branch, New Jersey, 미국, 07740
- Monmouth Medical Center
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Morristown, New Jersey, 미국, 07962
- Morristown Memorial Hospital
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New York
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Albany, New York, 미국, 12208
- Albany Medical College
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Buffalo, New York, 미국, 14222
- Women and Children's Hospital of Buffalo
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Hawthorne, New York, 미국, 10532
- New York Medical College
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New York, New York, 미국, 10032
- Columbia University Medical Center
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New York City, New York, 미국, 10003
- The CF Center, Beth Israel Medical Center
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Ohio
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Akron, Ohio, 미국, 44308
- Akron Children's Hospital
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Cincinnati, Ohio, 미국, 45229
- Cincinnati Children's Hospital
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Toledo, Ohio, 미국, 43606
- Toldedo Children's Hospital
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Oklahoma
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Oklahoma City, Oklahoma, 미국, 73104
- University of Oklahoma Health Sciences Center
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Pennsylvania
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Hershey, Pennsylvania, 미국, 17033
- Hershey Medical Center
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Philadelphia, Pennsylvania, 미국, 19134
- St. Christopher's Hospital for Children
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South Carolina
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Charleston, South Carolina, 미국, 29425
- Medical University of South Carolina
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Tennessee
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Memphis, Tennessee, 미국, 38103
- University of Tennessee
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Texas
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Fort Worth, Texas, 미국, 76104
- Cook Children's Medical Center
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Utah
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Salt Lake City, Utah, 미국, 84132
- Univeristy of Utah
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Vermont
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Colchester, Vermont, 미국, 05446
- Vermont Lung Center at the University of Vermont
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Virginia
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Richmond, Virginia, 미국, 23298
- Medical College of Virginia
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
12년 이상 (어린이, 성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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)
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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위약 비교기: 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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태블릿
Tablet
다른 이름들:
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실험적: 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
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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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
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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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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
기간: 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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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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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
기간: 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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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
기간: 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
기간: 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
기간: 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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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 수석 연구원: Patrick A Flume, MD, Medical University of South Carolina
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2009년 9월 1일
기본 완료 (실제)
2010년 7월 1일
연구 완료 (실제)
2013년 5월 1일
연구 등록 날짜
최초 제출
2009년 8월 4일
QC 기준을 충족하는 최초 제출
2009년 8월 5일
처음 게시됨 (추정)
2009년 8월 6일
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
2015년 9월 11일
QC 기준을 충족하는 마지막 업데이트 제출
2015년 8월 27일
마지막으로 확인됨
2015년 8월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .