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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
312
Cohort 1: Safety and Tolerability Based on Adverse Events (AEs)
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).
Time frame: Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21)
Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs)
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).
Time frame: Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56)
Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs
AEs and SAEs are defined in Outcome Measure 1.
Time frame: Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)
Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21
Time frame: Cohort 1: Day 14, Day 21
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Matching placebo tablet.
Unnamed facility
Birmingham, Alabama, United States
Unnamed facility
Anchorage, Alaska, United States
Unnamed facility
La Jolla, California, United States
Unnamed facility
Long Beach, California, United States
Unnamed facility
Palo Alto, California, United States
Unnamed facility
Sacramento, California, United States
Unnamed facility
Denver, Colorado, United States
Unnamed facility
New Haven, Connecticut, United States
Unnamed facility
Miami, Florida, United States
Unnamed facility
Orlando, Florida, United States
...and 45 more locations
Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56
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.
Time frame: Cohort 4: Baseline, Day 56
Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14
Time frame: Cohort 1: Baseline, Day 14
Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14
Time frame: Cohort 2: Baseline, Day 14
Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56
Time frame: Cohort 4: Baseline, Day 56
Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: Cohort 1: Day 14, Day 21
Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Time frame: Cohort 1: Day 14, Day 21
Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Time frame: Cohort 2 and 3: Day 28, Day 56
Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Time frame: Cohort 2 and 3: Day 28, Day 56
Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Time frame: Cohort 2 and 3: Baseline, Day 28 and 56
Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Time frame: Cohort 2 and 3: Baseline, Day 28 and 56
Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Time frame: Cohort 4: Baseline, Day 56
Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56
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.
Time frame: Cohort 2 and 3: Day 28, Day 56
Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56
CFQ-R respiratory domain is defined in Outcome Measure 17.
Time frame: Cohort 4: Baseline, Day 56
Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56
BMI was defined as weight in kilogram (kg) divided by height\*height in square meter (m\^2).
Time frame: Cohort 4: Baseline, Day 56
Cohort 4: Absolute Change From Baseline in Weight at Day 56
Time frame: Cohort 4: Baseline, Day 56