Cystic Fibrosis
Conditions
Keywords
Fibrosis, Pancreatic Diseases, Digestive System Diseases, Lung Diseases, Respiratory Tract Diseases, Genetic Diseases, Inborn, Infant, Newborn, Diseases, Pathologic Processes
Brief summary
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.
Detailed description
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.
Interventions
DRUGIvacaftor
Tablet
DRUGPlacebo
Tablet
Sponsors
Cystic Fibrosis Foundation
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16 | 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 : Rate of Change From Baseline in Weight Through Week 16 | 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 B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64 | 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. |
| Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64 | Part A baseline through Week 64 | ppFEV1 is defined in Outcome Measure 1. |
| Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64 | Part B baseline through Week 64 | ppFEV1 is defined in Outcome Measure 1. |
| Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16 | 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 B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64 | 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. |
| Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64 | 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. |
| Part B : Number of Participants With Pulmonary Exacerbations | 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 : Number of Pulmonary Exacerbation Events | 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 : Number of Pulmonary Exacerbation Events Per Participant Per Year | 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 : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo - Part A Placebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period). | 28 |
| Ivacaftor - Part A Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period). | 112 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part A (16-Week Double-Blind Treatment) | Adverse Event | 2 | 3 | 0 | 0 |
| Part A (16-Week Double-Blind Treatment) | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Part A (16-Week Double-Blind Treatment) | Noncompliance with Study Requirements | 0 | 2 | 0 | 0 |
| Part A (16-Week Double-Blind Treatment) | Required Prohibited Medication | 0 | 1 | 0 | 0 |
| Part A (16-Week Double-Blind Treatment) | Sponsor Decision | 0 | 1 | 0 | 0 |
| Part B (96-Week Open-Label Extension) | Adverse Event | 0 | 0 | 0 | 2 |
| Part B (96-Week Open-Label Extension) | Noncompliance with Study Requirements | 0 | 0 | 0 | 1 |
| Part B (96-Week Open-Label Extension) | Other | 0 | 0 | 0 | 2 |
| Part B (96-Week Open-Label Extension) | Required Prohibited Medication | 0 | 0 | 0 | 1 |
| Part B (96-Week Open-Label Extension) | Study Termination by Sponsor | 0 | 0 | 4 | 25 |
| Part B (96-Week Open-Label Extension) | Withdrawal by Subject | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Ivacaftor - Part A | Placebo - Part A | Total |
|---|---|---|---|
| Age, Continuous | 22.8 years STANDARD_DEVIATION 10.26 | 25.0 years STANDARD_DEVIATION 8.35 | 23.2 years STANDARD_DEVIATION 9.91 |
| Age, Customized 12 to 17 Years | 44 participants | 6 participants | 50 participants |
| Age, Customized 18 to 24 Years | 32 participants | 10 participants | 42 participants |
| Age, Customized 25 to 39 Years | 26 participants | 12 participants | 38 participants |
| Age, Customized 40 to 45 Years | 5 participants | 0 participants | 5 participants |
| Age, Customized > 45 Years | 5 participants | 0 participants | 5 participants |
| Body Mass Index | 21.2 kilogram per square meter STANDARD_DEVIATION 3.25 | 22.2 kilogram per square meter STANDARD_DEVIATION 4.48 | 21.4 kilogram per square meter STANDARD_DEVIATION 3.54 |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1), Continuous | 79.7 percent predicted of FEV1 STANDARD_DEVIATION 22.67 | 74.8 percent predicted of FEV1 STANDARD_DEVIATION 24.06 | 78.7 percent predicted of FEV1 STANDARD_DEVIATION 22.95 |
| ppFEV1, Categorical < 70% | 38 participants | 15 participants | 53 participants |
| ppFEV1, Categorical ≥ 70% to ≤ 90% | 35 participants | 5 participants | 40 participants |
| ppFEV1, Categorical > 90% | 39 participants | 8 participants | 47 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 110 participants | 27 participants | 137 participants |
| Race/Ethnicity, Customized White | 111 participants | 28 participants | 139 participants |
| Sex: Female, Male Female | 54 Participants | 12 Participants | 66 Participants |
| Sex: Female, Male Male | 58 Participants | 16 Participants | 74 Participants |
| Sweat Chloride | 101.4 millimoles per liter STANDARD_DEVIATION 10.28 | 102.4 millimoles per liter STANDARD_DEVIATION 7.91 | 101.6 millimoles per liter STANDARD_DEVIATION 9.83 |
| Weight | 58.2 kilograms STANDARD_DEVIATION 13.49 | 63.2 kilograms STANDARD_DEVIATION 14.96 | 59.2 kilograms STANDARD_DEVIATION 13.89 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 25 / 28 | 98 / 112 | 5 / 5 | 30 / 33 |
| serious Total, serious adverse events | 6 / 28 | 15 / 112 | 2 / 5 | 14 / 33 |
Outcome results
Primary
Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) 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.
Time frame: Part A baseline through Week 16
Population: Part A Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug during Part A. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Part A | Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16 | -0.2 percent predicted of FEV1 | Standard Error 1.1 |
| Ivacaftor - Part A | Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16 | 1.5 percent predicted of FEV1 | Standard Error 0.5 |
Comparison: The primary analysis for the primary efficacy variable was based on a Mixed-Effects Model for Repeated Measures (MMRM). The model included absolute change from baseline in percent predicted forced expiratory volume in 1 second (FEV1) as the dependent variable, treatment (ivacaftor versus placebo) and visit as fixed effects, and participant as a random effect, with adjustment for age and continuous baseline value of percent predicted FEV1.p-value: 0.150995% CI: [-0.6, 4.1]Mixed Models Analysis
Secondary
Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score 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.
Time frame: Part A baseline through Week 16
Population: Part A FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Part A | Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16 | -1.4 units on a scale | Standard Error 1.9 |
| Ivacaftor - Part A | Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16 | -0.1 units on a scale | Standard Error 1 |
Comparison: Analysis for the respiratory domain score endpoint was similar to that of the primary analysis of the primary efficacy endpoint. Estimates were from Mixed-Effects Model for Repeated Measures (MMRM) with the dependent variable being absolute change from baseline, fixed effects for categorical visit and treatment group, and adjustment for for age and baseline value for CFQ-R score, using unstructured covariance matrixp-value: 0.540895% CI: [-2.9, 5.6]Mixed Models Analysis
Secondary
Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration 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.
Time frame: Part A baseline through Week 16
Population: Part A FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Part A | Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16 | 0.1 millimole per liter (mmol/L) | Standard Error 1.2 |
| Ivacaftor - Part A | Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16 | -2.7 millimole per liter (mmol/L) | Standard Error 0.6 |
Comparison: Analysis for this variable was similar to that of the primary analysis of the primary efficacy endpoint. Estimates were from Mixed-Effects Model for Repeated Measures (MMRM) with dependent variable being absolute change from baseline, fixed effects for categorical visit and treatment group, and adjustment for continuous age and baseline value for age, sweat chloride, using unstructured covariance matrix.p-value: 0.038495% CI: [-5.6, -0.2]Mixed Models Analysis
Secondary
Part A : Rate of Change From Baseline in Weight 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.
Time frame: Part A baseline through Week 16
Population: Part A FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Part A | Part A : Rate of Change From Baseline in Weight Through Week 16 | 0.9 kilograms per 112 days | Standard Error 0.4 |
| Ivacaftor - Part A | Part A : Rate of Change From Baseline in Weight Through Week 16 | 0.8 kilograms per 112 days | Standard Error 0.2 |
Comparison: The analysis used the linear mixed model with treatment as fixed effects, visit (days on study) and treatment by visit interaction as random effects, with adjustment for age group (\< 18 years and ≥ 18 years) and percent predicted forced expiratory volume (FEV1) severity (\< 70%, ≥ 70% to ≤ 90%, \> 90%) at screening, with random intercept and random slope. Rate of change in the study period is the slope of weight versus time (days) multiplied by the number of days in the study period (112 days).p-value: 0.726595% CI: [-1.1, 0.7]Mixed Models Analysis
Secondary
Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through 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.
Time frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
Population: Part B FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo - Part A | Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64 | Change From Part A Baseline at Week 64 | 2.10 units on a scale | Standard Deviation 11.443 |
| Placebo - Part A | Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64 | Change From Part B Baseline at Week 64 | 2.08 units on a scale | Standard Deviation 17.763 |
| Ivacaftor - Part A | Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64 | Change From Part B Baseline at Week 64 | 2.62 units on a scale | Standard Deviation 15.899 |
| Ivacaftor - Part A | Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64 | Change From Part A Baseline at Week 64 | 1.50 units on a scale | Standard Deviation 15.778 |
Secondary
Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64
ppFEV1 is defined in Outcome Measure 1.
Time frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
Population: Part B FAS included all participants who received at least 1 dose of study drug during Part B. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo - Part A | Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64 | Change From Part A Baseline at Week 64 | 8.9398 percent predicted of FEV1 | Standard Deviation 9.703 |
| Placebo - Part A | Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64 | Change From Part B Baseline at Week 64 | 3.5593 percent predicted of FEV1 | Standard Deviation 7.95875 |
| Ivacaftor - Part A | Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64 | Change From Part A Baseline at Week 64 | 2.7233 percent predicted of FEV1 | Standard Deviation 10.52046 |
| Ivacaftor - Part A | Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64 | Change From Part B Baseline at Week 64 | -5.0565 percent predicted of FEV1 | Standard Deviation 11.44783 |
Secondary
Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through 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.
Time frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
Population: Part B FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo - Part A | Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64 | Change From Part A Baseline at Week 64 | -7.13 mmol/L | Standard Deviation 15.612 |
| Placebo - Part A | Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64 | Change From Part B Baseline at Week 64 | -3.88 mmol/L | Standard Deviation 7.685 |
| Ivacaftor - Part A | Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64 | Change From Part A Baseline at Week 64 | -3.65 mmol/L | Standard Deviation 11.963 |
| Ivacaftor - Part A | Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64 | Change From Part B Baseline at Week 64 | -2.44 mmol/L | Standard Deviation 11.037 |
Secondary
Part B : Absolute Change From Part A and Part B Baseline in Weight Through 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.
Time frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
Population: Part B FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo - Part A | Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64 | Change From Part A Baseline at Week 64 | 3.00 kilograms (kg) | Standard Deviation 3.55 |
| Placebo - Part A | Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64 | Change From Part B Baseline at Week 64 | 1.28 kilograms (kg) | Standard Deviation 2.243 |
| Ivacaftor - Part A | Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64 | Change From Part A Baseline at Week 64 | 2.35 kilograms (kg) | Standard Deviation 5.6 |
| Ivacaftor - Part A | Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64 | Change From Part B Baseline at Week 64 | 1.45 kilograms (kg) | Standard Deviation 3.84 |
Secondary
Part B : Number of Participants With Pulmonary Exacerbations
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.
Time frame: Part B baseline through Week 64
Population: Part B FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo - Part A | Part B : Number of Participants With Pulmonary Exacerbations | 4 participants |
| Ivacaftor - Part A | Part B : Number of Participants With Pulmonary Exacerbations | 16 participants |
Secondary
Part B : Number of Pulmonary Exacerbation Events
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.
Time frame: Part B baseline through Week 64
Population: Part B FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo - Part A | Part B : Number of Pulmonary Exacerbation Events | 6 events |
| Ivacaftor - Part A | Part B : Number of Pulmonary Exacerbation Events | 26 events |
Secondary
Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year
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.
Time frame: Part B baseline through Week 64
Population: Part B FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo - Part A | Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year | 1.10 events per participant per year |
| Ivacaftor - Part A | Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year | 0.82 events per participant per year |
Secondary
Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64
ppFEV1 is defined in Outcome Measure 1.
Time frame: Part A baseline through Week 64
Population: Part B FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Part A | Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64 | 5.7445 percent predicted of FEV1 per 448 days | Standard Error 3.681 |
| Ivacaftor - Part A | Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64 | -1.0738 percent predicted of FEV1 per 448 days | Standard Error 1.5025 |
Secondary
Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64
ppFEV1 is defined in Outcome Measure 1.
Time frame: Part B baseline through Week 64
Population: Part B FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Part A | Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64 | 5.3409 percent predicted of FEV1 per 336 days | Standard Error 4.579 |
| Ivacaftor - Part A | Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64 | -5.2994 percent predicted of FEV1 per 336 days | Standard Error 1.8871 |