Cystic Fibrosis
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis (CF) who have a non-G551D cystic fibrosis transmembrane regulator (CFTR) gating mutation (any one of the following CFTR mutations: G178R, G551S, S549N, S549R, G970R, G1244E, S1251N, S1255P, or G1349D).
Detailed description
Ivacaftor is the first CFTR modulator to show an improvement in CFTR function and clinical benefit in subjects with CF. Results from Phase 3 studies (VX08-770-102 \[Study 102\] \[NCT00909532\] and VX08-770-103 \[Study 103\] \[NCT00909727\]) showed that ivacaftor is effective in the treatment of subjects with CF who have the G551D-CFTR mutation, as evidenced by sustained improvements in CFTR channel function (measured by reduction in sweat chloride concentration) and corresponding substantial, durable improvements in lung function, pulmonary exacerbations, respiratory symptoms, and weight gain. Ivacaftor was also well tolerated, as evidenced by the rates and reasons for premature discontinuation and results of safety assessments. Ivacaftor (Trade Name Kalydeco; 150 mg tablets) was initially approved in the United States for the treatment of CF in subjects 6 years of age and older who have a G551D mutation in the CFTR gene.
Interventions
DRUGIvacaftor
150 mg tablet, oral use, administered twice a day (q12h)
DRUGPlacebo
oral use, administered twice a day (q12h)
Sponsors
Cystic Fibrosis Foundation
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female with confirmed diagnosis of CF * At least 1 allele of the following CFTR gating mutations: G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, G1349D * Percent predicted forced expiratory volume in 1 second (FEV1) greater than or equal to (\>=) 40 percent (%) predicted normal for age, sex, and height * 6 years of age or older * Minimum weight of 15 kilogram (kg) at screening * Females of childbearing potential must not be pregnant * Willing to comply with contraception requirements
Exclusion criteria
* G551D-CFTR mutation on at least 1 allele * History of any illness or condition that might confound the results of the study or pose an additional risk in administering ivacaftor to the subject * An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before the first dose of study drug * History of solid organ or hematological transplantation * History of alcohol, medication or illicit drug abuse within 1 year before the first dose of study drug * Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days before screening * Use of inhaled hypertonic saline treatment * Use of any inhibitors or inducers of cytochrome (CYP) P450 3A * Evidence of cataract or lens opacity at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 | Part 1: Baseline (pre-dose Day 1), Week 8 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1. |
| Part 2: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through 24 Weeks of Treatment (Week 36 Visit) | Baseline (pre-dose Week 12), Week 36 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years. Absolute change in percent predicted FEV1 over 24 weeks of ivacaftor treatment (from Week 12 \[Part 1: Treatment Period 2\] through Week 36 \[Part 2\]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2, as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Change From Baseline in Sweat Chloride Through Week 8 | Part 1: Baseline (pre-dose Day 1), Week 8 | Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (\>=) 15 microliter was required for determination of sweat chloride. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1. |
| Part 2: Change From Baseline in Sweat Chloride Through 24 Weeks of Treatment (Week 36 Visit) | Baseline (pre-dose Week 12), Week 36 | Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (\>=) 15 microliter was required for determination of sweat chloride. Change in sweat chloride over 24 weeks of ivacaftor treatment (from Week 12 \[Part 1: Treatment Period 2\] through Week 36 \[Part 2\]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2. |
| Part 1: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8 | Part 1: Baseline (pre-dose Day 1), Week 8 | The CFQ-R is a validated patient-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. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1. |
| Part 1: Change From Baseline in Body Mass Index (BMI) at Week 8 | Part 1: Baseline (pre-dose Day 1), Week 8 | BMI was defined as weight in kilogram (kg) divided by height in meters\^2 (m\^2). Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1. |
| Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Part 1: From signing of informed consent up to Week 20 | AE: any adverse change from subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. |
| Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Part 2: Week 20 up to Week 40 | AE: any adverse change from subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. |
| Part 2: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through 24 Weeks of Treatment (Week 36 Visit) | Baseline (pre-dose Week 12), Week 36 | The CFQ-R is a validated patient-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. Change in CFQ-R respiratory domain score over 24 weeks of ivacaftor treatment (from Week 12 \[Part 1: Treatment Period 2\] through Week 36 \[Part 2\]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2. |
| Part 2: Change From Baseline in Body Mass Index (BMI) at 24 Weeks of Treatment (Week 36 Visit) | Baseline (pre-dose Week 12), Week 36 | BMI was defined as weight in kg divided by height in m\^2. Change in BMI over 24 weeks of ivacaftor treatment (from Week 12 \[Part 1: Treatment Period 2\] through Week 36 \[Part 2\]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2. |
Countries
Belgium, France, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Ivacaftor First, Then Placebo Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period. | 20 |
| Part 1: Placebo First, Then Ivacaftor Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period. | 19 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part 1: Treatment Period 1 (8 Weeks) | Lost to Follow-up | 1 | 0 | 0 |
| Part 1: Treatment Period 1 (8 Weeks) | Need to extend washout period | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1: Ivacaftor First, Then Placebo | Part 1: Placebo First, Then Ivacaftor | Total |
|---|---|---|---|
| Age, Continuous | 23.8 years STANDARD_DEVIATION 13.25 | 21.7 years STANDARD_DEVIATION 12.92 | 22.8 years STANDARD_DEVIATION 12.96 |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 17 Participants |
| Sex: Female, Male Male | 13 Participants | 9 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 27 / 38 | 30 / 37 | 30 / 36 |
| serious Total, serious adverse events | 4 / 38 | 7 / 37 | 3 / 36 |
Outcome results
Primary
Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
Time frame: Part 1: Baseline (pre-dose Day 1), Week 8
Population: FAS for Part 1: all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo). Here, n signifies those subjects who were evaluable for this measure at given time point for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Ivacaftor | Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 | Baseline (n=38, 37) | 76.3659 percent predicted of FEV1 | Standard Deviation 20.3345 |
| Part 1: Ivacaftor | Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 | Change Through Week 8 (n=37, 37) | 8.1308 percent predicted of FEV1 | Standard Deviation 9.94676 |
| Part 1: Placebo | Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 | Baseline (n=38, 37) | 79.3361 percent predicted of FEV1 | Standard Deviation 20.83991 |
| Part 1: Placebo | Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 | Change Through Week 8 (n=37, 37) | -5.8738 percent predicted of FEV1 | Standard Deviation 7.23722 |
p-value: <0.000195% CI: [7.2559, 14.1]Mixed Models Analysis
Primary
Part 2: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through 24 Weeks of Treatment (Week 36 Visit)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years. Absolute change in percent predicted FEV1 over 24 weeks of ivacaftor treatment (from Week 12 \[Part 1: Treatment Period 2\] through Week 36 \[Part 2\]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2, as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
Time frame: Baseline (pre-dose Week 12), Week 36
Population: FAS for Part 2: all randomized subjects who received at least 1 dose of study drug (ivacaftor). Only subjects who were randomized to receive ivacaftor during Part 1: Treatment Period 2 were to be analyzed for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Ivacaftor | Part 2: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through 24 Weeks of Treatment (Week 36 Visit) | Baseline | 74.8375 percent predicted of FEV1 | Standard Deviation 19.36754 |
| Part 1: Ivacaftor | Part 2: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through 24 Weeks of Treatment (Week 36 Visit) | Change Through Week 36 | 13.5307 percent predicted of FEV1 | Standard Deviation 10.18174 |
Secondary
Part 1: Change From Baseline in Body Mass Index (BMI) at Week 8
BMI was defined as weight in kilogram (kg) divided by height in meters\^2 (m\^2). Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
Time frame: Part 1: Baseline (pre-dose Day 1), Week 8
Population: FAS for Part 1: all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo). Here, n signifies those subjects who were evaluable for this measure at given time point for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Ivacaftor | Part 1: Change From Baseline in Body Mass Index (BMI) at Week 8 | Baseline (n=38, 37) | 22.241 kg/m^2 | Standard Deviation 5.188 |
| Part 1: Ivacaftor | Part 1: Change From Baseline in Body Mass Index (BMI) at Week 8 | Change at Week 8 (n=37, 37) | 0.748 kg/m^2 | Standard Deviation 0.5793 |
| Part 1: Placebo | Part 1: Change From Baseline in Body Mass Index (BMI) at Week 8 | Change at Week 8 (n=37, 37) | 0.043 kg/m^2 | Standard Deviation 0.698 |
| Part 1: Placebo | Part 1: Change From Baseline in Body Mass Index (BMI) at Week 8 | Baseline (n=38, 37) | 22.527 kg/m^2 | Standard Deviation 4.9956 |
p-value: <0.000195% CI: [0.3366, 0.9881]Mixed Models Analysis
Secondary
Part 1: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8
The CFQ-R is a validated patient-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. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
Time frame: Part 1: Baseline (pre-dose Day 1), Week 8
Population: FAS for Part 1: all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo). Here, n signifies those subjects who were evaluable for this measure at given time point for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Ivacaftor | Part 1: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8 | Baseline (n=38, 37) | 70.61 units on a scale | Standard Deviation 17.409 |
| Part 1: Ivacaftor | Part 1: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8 | Change Through Week 8 (n=37, 37) | 12.31 units on a scale | Standard Deviation 16.891 |
| Part 1: Placebo | Part 1: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8 | Baseline (n=38, 37) | 74.55 units on a scale | Standard Deviation 20.616 |
| Part 1: Placebo | Part 1: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8 | Change Through Week 8 (n=37, 37) | -2.33 units on a scale | Standard Deviation 20.648 |
p-value: 0.000495% CI: [4.4874, 14.7336]Mixed Models Analysis
Secondary
Part 1: Change From Baseline in Sweat Chloride Through Week 8
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (\>=) 15 microliter was required for determination of sweat chloride. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
Time frame: Part 1: Baseline (pre-dose Day 1), Week 8
Population: FAS for Part 1: all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo). Here, n signifies those subjects who were evaluable for this measure at given time point for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Ivacaftor | Part 1: Change From Baseline in Sweat Chloride Through Week 8 | Change Through Week 8 (n=36, 36) | -55.82 millimole per liter (mmol/L) | Standard Deviation 24.89 |
| Part 1: Ivacaftor | Part 1: Change From Baseline in Sweat Chloride Through Week 8 | Baseline (n=38, 37) | 93.37 millimole per liter (mmol/L) | Standard Deviation 18.099 |
| Part 1: Placebo | Part 1: Change From Baseline in Sweat Chloride Through Week 8 | Change Through Week 8 (n=36, 36) | -5.63 millimole per liter (mmol/L) | Standard Deviation 9.833 |
| Part 1: Placebo | Part 1: Change From Baseline in Sweat Chloride Through Week 8 | Baseline (n=38, 37) | 94.23 millimole per liter (mmol/L) | Standard Deviation 20.581 |
p-value: <0.000195% CI: [-56.9527, -41.3807]Mixed Models Analysis
Secondary
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any adverse change from subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.
Time frame: Part 1: From signing of informed consent up to Week 20
Population: Safety Set for Part 1 included all subjects who received at least 1 dose of study drug (ivacaftor or placebo).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Ivacaftor | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 28 participants |
| Part 1: Ivacaftor | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 4 participants |
| Part 1: Placebo | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 31 participants |
| Part 1: Placebo | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 7 participants |
Secondary
Part 2: Change From Baseline in Body Mass Index (BMI) at 24 Weeks of Treatment (Week 36 Visit)
BMI was defined as weight in kg divided by height in m\^2. Change in BMI over 24 weeks of ivacaftor treatment (from Week 12 \[Part 1: Treatment Period 2\] through Week 36 \[Part 2\]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
Time frame: Baseline (pre-dose Week 12), Week 36
Population: FAS for Part 2: all randomized subjects who received at least 1 dose of study drug (ivacaftor). Only subjects who were randomized to receive ivacaftor during Part 1: Treatment Period 2 were to be analyzed for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Ivacaftor | Part 2: Change From Baseline in Body Mass Index (BMI) at 24 Weeks of Treatment (Week 36 Visit) | Baseline | 22.222 kg/m^2 | Standard Deviation 6.2919 |
| Part 1: Ivacaftor | Part 2: Change From Baseline in Body Mass Index (BMI) at 24 Weeks of Treatment (Week 36 Visit) | Change at Week 36 | 1.263 kg/m^2 | Standard Deviation 0.7588 |
Secondary
Part 2: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through 24 Weeks of Treatment (Week 36 Visit)
The CFQ-R is a validated patient-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. Change in CFQ-R respiratory domain score over 24 weeks of ivacaftor treatment (from Week 12 \[Part 1: Treatment Period 2\] through Week 36 \[Part 2\]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
Time frame: Baseline (pre-dose Week 12), Week 36
Population: FAS for Part 2: all randomized subjects who received at least 1 dose of study drug (ivacaftor). Only subjects who were randomized to receive ivacaftor during Part 1: Treatment Period 2 were to be analyzed for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Ivacaftor | Part 2: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through 24 Weeks of Treatment (Week 36 Visit) | Baseline | 71.30 units on a scale | Standard Deviation 19.526 |
| Part 1: Ivacaftor | Part 2: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through 24 Weeks of Treatment (Week 36 Visit) | Change Through Week 36 | 11.42 units on a scale | Standard Deviation 13.604 |
Secondary
Part 2: Change From Baseline in Sweat Chloride Through 24 Weeks of Treatment (Week 36 Visit)
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (\>=) 15 microliter was required for determination of sweat chloride. Change in sweat chloride over 24 weeks of ivacaftor treatment (from Week 12 \[Part 1: Treatment Period 2\] through Week 36 \[Part 2\]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
Time frame: Baseline (pre-dose Week 12), Week 36
Population: FAS for Part 2: all randomized subjects who received at least 1 dose of study drug (ivacaftor). Only subjects who were randomized to receive ivacaftor during Part 1: Treatment Period 2 were to be analyzed for this measure. Here n signifies those subjects who were evaluable for this measure at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Ivacaftor | Part 2: Change From Baseline in Sweat Chloride Through 24 Weeks of Treatment (Week 36 Visit) | Baseline (n=18) | 92.03 mmol/L | Standard Deviation 11.468 |
| Part 1: Ivacaftor | Part 2: Change From Baseline in Sweat Chloride Through 24 Weeks of Treatment (Week 36 Visit) | Change Through Week 36 (n=17) | -59.24 mmol/L | Standard Deviation 32.566 |
Secondary
Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any adverse change from subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.
Time frame: Part 2: Week 20 up to Week 40
Population: Safety Set for Part 2 included all subjects who received at least 1 dose of study drug (ivacaftor).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Ivacaftor | Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 3 participants |
| Part 1: Ivacaftor | Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 30 participants |