- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01225211
Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation
September 2, 2015 updated by: Vertex Pharmaceuticals Incorporated
A Phase 2, Multicenter, Double-Blinded, Placebo-Controlled, Multiple-Dose Study to Evaluate Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Lumacaftor Monotherapy, and Lumacaftor and Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
The purpose of this study is to evaluate of the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of lumacaftor (VX-809) alone and when coadministered with ivacaftor (VX-770) in participants with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
312
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Adelaide, Australia
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Brisbane, Australia
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Chermside, Australia
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Nedlands, Australia
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Parkville Victoria, Australia
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Westmead, Australia
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Leuven, Belgium
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Paris, France
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Rhone
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Pierre Benite Cedex, Rhone, France
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Berlin, Germany
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Bochum, Germany
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Essen, Germany
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Koeln, Germany
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Thueringen
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Jena, Thueringen, Germany
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Auckland, New Zealand
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Christchurch, New Zealand
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London, United Kingdom
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Alabama
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Birmingham, Alabama, United States
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Alaska
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Anchorage, Alaska, United States
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California
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La Jolla, California, United States
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Long Beach, California, United States
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Palo Alto, California, United States
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Sacramento, California, United States
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Colorado
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Denver, Colorado, United States
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Connecticut
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New Haven, Connecticut, United States
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Florida
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Miami, Florida, United States
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Orlando, Florida, United States
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Tampa, Florida, United States
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Georgia
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Atlanta, Georgia, United States
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Idaho
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Boise, Idaho, United States
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Illinois
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Chicago, Illinois, United States
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Iowa
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Iowa City, Iowa, United States
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Kansas
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Kansas City, Kansas, United States
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Kentucky
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Lexington, Kentucky, United States
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Louisiana
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New Orleans, Louisiana, United States
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Maryland
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Baltimore, Maryland, United States
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Massachusetts
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Boston, Massachusetts, United States
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Minnesota
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Minneapolis, Minnesota, United States
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Missouri
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St. Louis, Missouri, United States
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Nebraska
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Omaha, Nebraska, United States
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New Hampshire
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Lebanon, New Hampshire, United States
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New York
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Buffalo, New York, United States
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New Hyde Park, New York, United States
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New York, New York, United States
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Rochester, New York, United States
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Syracuse, New York, United States
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North Carolina
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Chapel Hill, North Carolina, United States
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Ohio
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Akron, Ohio, United States
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Cleveland, Ohio, United States
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Columbus, Ohio, United States
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Oklahoma
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Oklahoma City, Oklahoma, United States
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Pennsylvania
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Philadelphia, Pennsylvania, United States
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Pittsburg, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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South Carolina
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Charleston, South Carolina, United States
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South Dakota
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Sioux Falls, South Dakota, United States
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female participants with confirmed diagnosis of CF
- Must have the F508del-CFTR mutation on at least 1 allele.
- FEV1 greater than equal (>=) 40% of predicted normal for age, gender, and height (Knudson standards)(Cohort 1, 2, and 3); FEV1 40-90% of predicted normal for age, gender, and height (Hankinson standards (Cohort 4)
- Participant of child-bearing potential and who are sexually active must meet the contraception requirements
Exclusion Criteria:
- History of any illness or condition that, in the opinion of the investigator might confound the results of the study or pose an additional risk in administering study drug to the participant (e.g., cirrhosis with portal hypertension).
- An acute illness including acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 14 days (Cohort 1, 2, and 3) or 28 days (Cohort 4) before receiving the first dose of study drug.
- History of solid organ or hematological transplantation.
- History of alcohol abuse or drug addiction in the past year, including cannabis, cocaine, and opiates.
- Ongoing participation in another therapeutic clinical study, or prior participation in an investigational drug study without appropriate washout
- Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception
- Participants enrolled in Cohort 1 or Cohort 2 will not be eligible for Cohort 3
- Ongoing or prior participation in an investigational drug study within 30 days of the Screening Visit
- Heterozygous participants who participated in Cohort 2 and meet the eligibility criteria for Cohort 4 may participate in Cohort 4
- Evidence of lens opacity or cataract as determined by the ophthalmologic examination (Cohort 4 only)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Cohort 1: Placebo
Participants homozygous (HO) for the F508del-CF transmembrane conductance regulator gene (CFTR) mutation received lumacaftor matched placebo once daily (qd) (Day 1 through Day 14), followed by lumacaftor matched placebo qd in combination with ivacaftor matched placebo every 12 hours (q12h) (Day 15 through Day 21).
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Matching placebo tablet.
Matching placebo tablet.
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Experimental: Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h
Participants homozygous for the F508del-CFTR mutation received 200 milligram (mg) of lumacaftor (LUM) qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor (IVA) q12h (Day 15 through Day 21).
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Tablet
Other Names:
Tablet.
Other Names:
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Experimental: Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h
Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21).
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Tablet
Other Names:
Tablet.
Other Names:
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Placebo Comparator: Cohort 2 and 3: Placebo (HO and HE)
Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).
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Matching placebo tablet.
Matching placebo tablet.
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Experimental: Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO)
Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
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Tablet
Other Names:
Tablet.
Other Names:
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Experimental: Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO)
Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
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Tablet
Other Names:
Tablet.
Other Names:
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Experimental: Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE)
Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
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Tablet
Other Names:
Tablet.
Other Names:
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Experimental: Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO)
Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
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Tablet
Other Names:
Tablet.
Other Names:
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Placebo Comparator: Cohort 4: Placebo
Participants heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 1 through Day 56).
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Matching placebo tablet.
Matching placebo tablet.
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Experimental: Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
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Tablet
Other Names:
Tablet.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Cohort 1: Safety and Tolerability Based on Adverse Events (AEs)
Time Frame: Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21)
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AE: any untoward medical occurrence in a participant during study; irrespective of relationship with treatment.
This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent.
AE includes serious AEs (SAEs) as well as Non-SAEs.
SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event.
Number of participants with AEs and SAEs are reported.
AE that started at/after initial dosing of study drug, or increased in severity after initial dosing of study drug is considered treatment-emergent.
Results are reported separately for monotherapy period (Period 1: Day 1 to Day 14) and combination therapy period (Period 2: Day 15 to Day 21).
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Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21)
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Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs)
Time Frame: Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56)
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Detailed description is provided in Outcome Measure 1. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 28) and combination therapy period (Period 2: Day 29 to Day 56).
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Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56)
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Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs
Time Frame: Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)
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AEs and SAEs are defined in Outcome Measure 1.
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Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)
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Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21
Time Frame: Cohort 1: Day 14, Day 21
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Cohort 1: Day 14, Day 21
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Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56
Time Frame: Cohort 2 and 3: Day 28, Day 56
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Cohort 2 and 3: Day 28, Day 56
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Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56
Time Frame: Cohort 4: Baseline, Day 56
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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 Hankinson method.
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Cohort 4: Baseline, Day 56
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14
Time Frame: Cohort 1: Baseline, Day 14
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Cohort 1: Baseline, Day 14
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Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14
Time Frame: Cohort 2: Baseline, Day 14
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Cohort 2: Baseline, Day 14
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Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56
Time Frame: Cohort 4: Baseline, Day 56
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Cohort 4: Baseline, Day 56
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Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21
Time Frame: Cohort 1: Day 14, Day 21
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FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
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Cohort 1: Day 14, Day 21
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Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21
Time Frame: Cohort 1: Day 14, Day 21
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FEV1 and ppFEV1 are defined in Outcome Measure 6.
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Cohort 1: Day 14, Day 21
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Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56
Time Frame: Cohort 2 and 3: Day 28, Day 56
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FEV1 and ppFEV1 are defined in Outcome Measure 6.
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Cohort 2 and 3: Day 28, Day 56
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Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56
Time Frame: Cohort 2 and 3: Day 28, Day 56
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FEV1 and ppFEV1 are defined in Outcome Measure 6.
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Cohort 2 and 3: Day 28, Day 56
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Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56
Time Frame: Cohort 2 and 3: Baseline, Day 28 and 56
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FEV1 and ppFEV1 are defined in Outcome Measure 6.
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Cohort 2 and 3: Baseline, Day 28 and 56
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Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56
Time Frame: Cohort 2 and 3: Baseline, Day 28 and 56
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FEV1 and ppFEV1 are defined in Outcome Measure 6.
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Cohort 2 and 3: Baseline, Day 28 and 56
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Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56
Time Frame: Cohort 4: Baseline, Day 56
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FEV1 and ppFEV1 are defined in Outcome Measure 6.
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Cohort 4: Baseline, Day 56
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Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56
Time Frame: Cohort 2 and 3: Day 28, Day 56
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The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for subjects 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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Cohort 2 and 3: Day 28, Day 56
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Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56
Time Frame: Cohort 4: Baseline, Day 56
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CFQ-R respiratory domain is defined in Outcome Measure 17.
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Cohort 4: Baseline, Day 56
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Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56
Time Frame: Cohort 4: Baseline, Day 56
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BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).
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Cohort 4: Baseline, Day 56
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Cohort 4: Absolute Change From Baseline in Weight at Day 56
Time Frame: Cohort 4: Baseline, Day 56
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Cohort 4: Baseline, Day 56
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
- Rowe SM, McColley SA, Rietschel E, Li X, Bell SC, Konstan MW, Marigowda G, Waltz D, Boyle MP; VX09-809-102 Study Group. Lumacaftor/Ivacaftor Treatment of Patients with Cystic Fibrosis Heterozygous for F508del-CFTR. Ann Am Thorac Soc. 2017 Feb;14(2):213-219. doi: 10.1513/AnnalsATS.201609-689OC.
- Boyle MP, Bell SC, Konstan MW, McColley SA, Rowe SM, Rietschel E, Huang X, Waltz D, Patel NR, Rodman D; VX09-809-102 study group. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med. 2014 Jul;2(7):527-38. doi: 10.1016/S2213-2600(14)70132-8. Epub 2014 Jun 24.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2010
Primary Completion (Actual)
April 1, 2014
Study Completion (Actual)
April 1, 2014
Study Registration Dates
First Submitted
October 15, 2010
First Submitted That Met QC Criteria
October 19, 2010
First Posted (Estimate)
October 20, 2010
Study Record Updates
Last Update Posted (Estimate)
October 5, 2015
Last Update Submitted That Met QC Criteria
September 2, 2015
Last Verified
September 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- VX09-809-102
- 2010-020413-90 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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