Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis
Brief summary
The purpose of this study is to provide information regarding the long-term safety and pharmacodynamics of ivacaftor treatment in the pediatric population younger than 6 years of age with Cystic Fibrosis (CF) who have a CFTR gating mutation in at least 1 allele and will further explore the efficacy of long-term ivacaftor treatment in this population of patients with CF.
Interventions
DRUGIvacaftor
Sponsors
Cystic Fibrosis Foundation
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(Ivacaftor Arm): 1. Completed the last study visit of the treatment period of the previous study (NCT01705145) 2. Hematology, serum chemistry, and vital signs results on Day 1 with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator 3. As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions and the parent or legal guardian should be able to ensure that the subject assents to participation in the study to the degree the subject can assent, and that the subject will comply with and is likely to complete the study as planned Inclusion Criteria (Observational Arm): 1\. Subjects who completed their assigned study drug treatment in the previous study (NCT01705145) and elected not to enroll in the ivacaftor arm and subjects who prematurely discontinued treatment in the previous study and received at least 1 dose of study drug treatment in the previous study will be eligible for enrollment in the observational arm.
Exclusion criteria
(Ivacaftor Arm): 1. Subjects who prematurely discontinued from the previous study 2. 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 subject 3. Subjects with a history of study treatment intolerance as observed in their previous study that, in the opinion of the investigator, might pose an additional risk in administering study drug to the subject 4. Subjects receiving commercially-available ivacaftor treatment 5. Subject was unable to complete an adequate slit-lamp examination at the last ophthalmologic examination in the previous study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Week 97 (for participants who completed study drug dosing); Day 1 up to 24 weeks after the last dose (up to Week 108, for participants who prematurely discontinued study drug dosing) | AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation was considered treatment-emergent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84 | Baseline (study 109), Week 24, 48, 72 and 84 (study 109) | Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of \>=15 microliter was required for determination of sweat chloride. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412). |
| Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109) | Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145) |
| Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109) | Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412). |
| Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84 | Baseline (study 108), Week 24, 48, 72 and 84 (study 109) | 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 measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145). |
| Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109) | Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412). |
| Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109) | BMI = (Weight \[in kg\]) divided by (Stature \[in meters\]) \^2. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145). |
| Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109) | BMI = (Weight \[in kg\]) divided by (Stature \[in meters\]) \^2. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412). |
| Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109) | Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145). |
Countries
Canada, United Kingdom, United States
Participant flow
Recruitment details
This was a Phase 3, multicenter, 2 arm study in participants who received at least 1 dose of study drug in parent study VX11-770-108 (study 108) (NCT01705145).
Pre-assignment details
In study VX11-770-109 (study 109) (NCT01946412), participants were to be enrolled in either ivacaftor arm or observational arm. However, there were no participants enrolled in the observational arm. A total of 33 participants were enrolled in the ivacaftor arm.
Participants by arm
| Arm | Count |
|---|---|
| Ivacaftor Participants received ivacaftor 50 mg or 75 mg or 150 mg based on body weight and age. Ivacaftor 50 mg administered q12h for participants aged 2 to \< 6 years and weighing \<14 kg, ivacaftor 75 mg q12h for participants aged 2 to \<6 years and weighing \>= 14 kg and ivacaftor 150 mg q12h for participants \>=6 years. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Continued with commercial Kalydeco | 2 |
| Overall Study | Difficulty in swallowing | 1 |
| Overall Study | Non-Compliance | 1 |
Baseline characteristics
| Characteristic | Ivacaftor |
|---|---|
| Age, Continuous | 3.7 years STANDARD_DEVIATION 1.04 |
| Gender Female | 6 Participants |
| Gender Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 9 | 24 / 24 |
| serious Total, serious adverse events | 6 / 9 | 5 / 24 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation was considered treatment-emergent.
Time frame: Day 1 up to Week 97 (for participants who completed study drug dosing); Day 1 up to 24 weeks after the last dose (up to Week 108, for participants who prematurely discontinued study drug dosing)
Population: Safety set included all participants who received at least 1 dose of study drug in study 109 (NCT01946412). As per the planned analysis for this study, participants were to be analyzed based on their dosing groups as per parent study VX11-770-108 (NCT01705145).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ivacaftor 50 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 9 participants |
| Ivacaftor 50 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 6 participants |
| Ivacaftor 75 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 24 participants |
| Ivacaftor 75 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 5 participants |
Secondary
Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84
BMI = (Weight \[in kg\]) divided by (Stature \[in meters\]) \^2. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145).
Time frame: Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
Population: Safety set. Here n signifies those participants who were evaluable at the specified time points for each arm, respectively. As per the planned analysis for this study, participants were to be analyzed based on their dosing groups as per parent study VX11-770-108 (NCT01705145).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (n=9, 24) | 15.74 Kilogram per square meter (kg/m^2) | Standard Deviation 0.69 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 12 (n=9, 23) | 0.03 Kilogram per square meter (kg/m^2) | Standard Deviation 0.4 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 24 (n=9, 23) | 0.31 Kilogram per square meter (kg/m^2) | Standard Deviation 0.57 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 36 (n=9, 23) | 0.15 Kilogram per square meter (kg/m^2) | Standard Deviation 0.52 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 48 (n=9, 22) | -0.31 Kilogram per square meter (kg/m^2) | Standard Deviation 0.6 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 60 (n=9, 22) | -0.12 Kilogram per square meter (kg/m^2) | Standard Deviation 0.7 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 72 (n=9, 20) | -0.38 Kilogram per square meter (kg/m^2) | Standard Deviation 0.68 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 84 (n=9, 19) | -0.16 Kilogram per square meter (kg/m^2) | Standard Deviation 0.96 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 84 (n=9, 19) | 0.28 Kilogram per square meter (kg/m^2) | Standard Deviation 0.97 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (n=9, 24) | 16.06 Kilogram per square meter (kg/m^2) | Standard Deviation 1.15 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 48 (n=9, 22) | -0.13 Kilogram per square meter (kg/m^2) | Standard Deviation 0.77 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 12 (n=9, 23) | 0.09 Kilogram per square meter (kg/m^2) | Standard Deviation 0.6 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 72 (n=9, 20) | 0.09 Kilogram per square meter (kg/m^2) | Standard Deviation 0.97 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 24 (n=9, 23) | -0.12 Kilogram per square meter (kg/m^2) | Standard Deviation 0.9 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 60 (n=9, 22) | -0.06 Kilogram per square meter (kg/m^2) | Standard Deviation 0.9 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 36 (n=9, 23) | 0.09 Kilogram per square meter (kg/m^2) | Standard Deviation 0.73 |
Secondary
Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84
Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145).
Time frame: Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
Population: Safety set. Here n signifies those participants who were evaluable at the specified time points for each arm, respectively. As per the planned analysis for this study, participants were to be analyzed based on their dosing groups as per parent study VX11-770-108 (NCT01705145).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (n=9, 24) | 89.1 Centimeters (cm) | Standard Deviation 4.3 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 12 (n=9, 23) | 4.6 Centimeters (cm) | Standard Deviation 1.2 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 24 (n=9, 23) | 6.0 Centimeters (cm) | Standard Deviation 1.7 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 36 (n=9, 23) | 7.8 Centimeters (cm) | Standard Deviation 1.8 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 48 (n=9, 21) | 9.7 Centimeters (cm) | Standard Deviation 2 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 60 (n=9, 22) | 11.0 Centimeters (cm) | Standard Deviation 2.2 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 72 (n=9, 20) | 12.5 Centimeters (cm) | Standard Deviation 2.6 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 84 (n=9, 19) | 13.6 Centimeters (cm) | Standard Deviation 2.3 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 84 (n=9, 19) | 15.0 Centimeters (cm) | Standard Deviation 2.3 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (n=9, 24) | 102.3 Centimeters (cm) | Standard Deviation 6.4 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 48 (n=9, 21) | 10.4 Centimeters (cm) | Standard Deviation 1.7 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 12 (n=9, 23) | 5.4 Centimeters (cm) | Standard Deviation 1.1 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 72 (n=9, 20) | 13.4 Centimeters (cm) | Standard Deviation 2 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 24 (n=9, 23) | 7.7 Centimeters (cm) | Standard Deviation 3.3 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 60 (n=9, 22) | 11.6 Centimeters (cm) | Standard Deviation 2 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change in Week 36 (n=9, 23) | 8.8 Centimeters (cm) | Standard Deviation 1.4 |
Secondary
Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84
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 measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145).
Time frame: Baseline (study 108), Week 24, 48, 72 and 84 (study 109)
Population: Safety set. Here n signifies those participants who were evaluable at the specified time points for each arm, respectively.As per the planned analysis for this study, participants were to be analyzed based on their dosing groups as per parent study VX11-770-108 (NCT01705145).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 24 (n=6,18) | -62.1 millimole per liter (mmol/L) | Standard Deviation 12.4 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 72 (n=7,14) | -46.4 millimole per liter (mmol/L) | Standard Deviation 16 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 48 (n=6,15) | -29.3 millimole per liter (mmol/L) | Standard Deviation 37.8 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 84 (n=6,14) | -46.5 millimole per liter (mmol/L) | Standard Deviation 31 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84 | Baseline (n=7,22) | 93.1 millimole per liter (mmol/L) | Standard Deviation 16.2 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 84 (n=6,14) | -58.1 millimole per liter (mmol/L) | Standard Deviation 23.9 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84 | Baseline (n=7,22) | 99.6 millimole per liter (mmol/L) | Standard Deviation 13.6 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 24 (n=6,18) | -48.5 millimole per liter (mmol/L) | Standard Deviation 18.4 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 48 (n=6,15) | -51.8 millimole per liter (mmol/L) | Standard Deviation 27.1 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 72 (n=7,14) | -52.9 millimole per liter (mmol/L) | Standard Deviation 26.7 |
Secondary
Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84
Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145)
Time frame: Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
Population: Safety set. Here n signifies those participants who were evaluable at the specified time points for each arm, respectively. As per the planned analysis for this study, participants were to be analyzed based on their dosing groups as per parent study VX11-770-108 (NCT01705145).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (n=9, 24) | 12.5 kilogram (kg) | Standard Deviation 1.1 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 12 (n= 9, 23) | 1.3 kilogram (kg) | Standard Deviation 0.4 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 24 (n=9, 23) | 2.0 kilogram (kg) | Standard Deviation 0.6 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 36 (n=9, 23) | 2.4 kilogram (kg) | Standard Deviation 0.7 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 48 (n=9, 22) | 2.6 kilogram (kg) | Standard Deviation 0.9 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 60 (n=9, 22) | 3.2 kilogram (kg) | Standard Deviation 1 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 72 (n=9, 20) | 3.4 kilogram (kg) | Standard Deviation 0.9 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 84 (n=9, 19) | 4.0 kilogram (kg) | Standard Deviation 1.2 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 84 (n=9, 19) | 5.7 kilogram (kg) | Standard Deviation 1.9 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (n=9, 24) | 16.8 kilogram (kg) | Standard Deviation 1.8 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 48 (n=9, 22) | 3.4 kilogram (kg) | Standard Deviation 1.1 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 12 (n= 9, 23) | 1.9 kilogram (kg) | Standard Deviation 0.7 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 72 (n=9, 20) | 4.8 kilogram (kg) | Standard Deviation 1.6 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 24 (n=9, 23) | 2.5 kilogram (kg) | Standard Deviation 0.9 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 60 (n=9, 22) | 4.0 kilogram (kg) | Standard Deviation 1.3 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 36 (n=9, 23) | 3.1 kilogram (kg) | Standard Deviation 1 |
Secondary
Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84
BMI = (Weight \[in kg\]) divided by (Stature \[in meters\]) \^2. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412).
Time frame: Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
Population: Safety set. Here n signifies those participants who were evaluable at the specified time points for each arm, respectively. As per the planned analysis for this study, participants were to be analyzed based on their dosing groups as per parent study VX11-770-108 (NCT01705145).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (n= 9, 24) | 16.07 kg/m^2 | Standard Deviation 0.55 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 12 (n= 9, 23) | -0.30 kg/m^2 | Standard Deviation 0.6 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 24 (n= 9, 23) | -0.02 kg/m^2 | Standard Deviation 0.7 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 36 (n= 9, 23) | -0.18 kg/m^2 | Standard Deviation 0.83 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 48 (n= 9, 22) | -0.64 kg/m^2 | Standard Deviation 0.81 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 60 (n= 9, 22) | -0.45 kg/m^2 | Standard Deviation 0.82 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 72 (n= 9, 20) | -0.71 kg/m^2 | Standard Deviation 0.9 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 84 (n= 9, 19) | -0.49 kg/m^2 | Standard Deviation 1.09 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 84 (n= 9, 19) | -0.01 kg/m^2 | Standard Deviation 0.87 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (n= 9, 24) | 16.33 kg/m^2 | Standard Deviation 1.12 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 48 (n= 9, 22) | -0.35 kg/m^2 | Standard Deviation 0.57 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 12 (n= 9, 23) | -0.16 kg/m^2 | Standard Deviation 0.48 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 72 (n= 9, 20) | -0.21 kg/m^2 | Standard Deviation 0.78 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 24 (n= 9, 23) | -0.36 kg/m^2 | Standard Deviation 1.03 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 60 (n= 9, 22) | -0.29 kg/m^2 | Standard Deviation 0.72 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 36 (n= 9, 23) | -0.16 kg/m^2 | Standard Deviation 0.63 |
Secondary
Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84
Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412).
Time frame: Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
Population: Safety set. Here n signifies those participants who were evaluable at the specified time points for each arm, respectively. As per the planned analysis for this study, participants were to be analyzed based on their dosing groups as per parent study VX11-770-108 (NCT01705145).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (n=9, 24) | 91.7 cm | Standard Deviation 4.3 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 12 (n=9, 23) | 2.0 cm | Standard Deviation 1.1 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 24 (n=9, 23) | 3.4 cm | Standard Deviation 1.2 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 36 (n=9, 23) | 5.2 cm | Standard Deviation 1.5 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 48 (n=9, 21) | 7.2 cm | Standard Deviation 1.3 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 60 (n=9, 22) | 8.4 cm | Standard Deviation 1.4 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 72 (n=9, 20) | 10.0 cm | Standard Deviation 2.1 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 84 (n=9, 19) | 11.1 cm | Standard Deviation 1.7 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 84 (n=9, 19) | 11.4 cm | Standard Deviation 1.9 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (n=9, 24) | 105.8 cm | Standard Deviation 6.6 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 48 (n=9, 21) | 6.8 cm | Standard Deviation 1.3 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 12 (n=9, 23) | 1.8 cm | Standard Deviation 0.9 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 72 (n=9, 20) | 9.8 cm | Standard Deviation 1.6 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 24 (n=9, 23) | 4.1 cm | Standard Deviation 3.2 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 60 (n=9, 22) | 8.0 cm | Standard Deviation 1.5 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 36 (n=9, 23) | 5.2 cm | Standard Deviation 1.1 |
Secondary
Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of \>=15 microliter was required for determination of sweat chloride. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412).
Time frame: Baseline (study 109), Week 24, 48, 72 and 84 (study 109)
Population: Safety set. Here n signifies those participants who were evaluable at the specified time points for each arm, respectively. As per the planned analysis for this study, participants were to be analyzed based on their dosing groups as per parent study VX11-770-108 (NCT01705145).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 24 (n=7,18) | -4.3 mmol/L | Standard Deviation 31.6 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 72 (n=8,15) | -1.5 mmol/L | Standard Deviation 24.3 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 48 (n=7,17) | 18.1 mmol/L | Standard Deviation 39.5 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 84 (n=7,16) | -2.4 mmol/L | Standard Deviation 44.2 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84 | Baseline (n= 8,23) | 47.8 mmol/L | Standard Deviation 23.3 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 84 (n=7,16) | -11.2 mmol/L | Standard Deviation 25.4 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84 | Baseline (n= 8,23) | 52.9 mmol/L | Standard Deviation 23.1 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 24 (n=7,18) | 3.4 mmol/L | Standard Deviation 15.9 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 48 (n=7,17) | -4.5 mmol/L | Standard Deviation 22.6 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84 | Absolute Change at Week 72 (n=8,15) | -6.0 mmol/L | Standard Deviation 20.8 |
Secondary
Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84
Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412).
Time frame: Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109)
Population: Safety set. Here n signifies those participants who were evaluable at the specified time points for each arm, respectively. As per the planned analysis for this study, participants were to be analyzed based on their dosing groups as per parent study VX11-770-108 (NCT01705145).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (n= 9, 24) | 13.5 Kg | Standard Deviation 1 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 48 (n=9, 22) | 1.6 Kg | Standard Deviation 0.7 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 24 (n=9, 23) | 1.0 Kg | Standard Deviation 0.5 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 60 (n=9, 22) | 2.2 Kg | Standard Deviation 0.8 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 12 (n=9, 23) | 0.3 Kg | Standard Deviation 0.4 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 72 (n=9, 20) | 2.4 Kg | Standard Deviation 0.7 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 36 (n=9, 23) | 1.4 Kg | Standard Deviation 0.6 |
| Ivacaftor 50 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 84 (n=9, 19) | 3.0 Kg | Standard Deviation 1 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 36 (n=9, 23) | 1.6 Kg | Standard Deviation 0.8 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline (n= 9, 24) | 18.3 Kg | Standard Deviation 2 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 12 (n=9, 23) | 0.4 Kg | Standard Deviation 0.5 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 24 (n=9, 23) | 1.0 Kg | Standard Deviation 0.7 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 84 (n=9, 19) | 4.2 Kg | Standard Deviation 1.7 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 48 (n=9, 22) | 1.9 Kg | Standard Deviation 0.8 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 60 (n=9, 22) | 2.5 Kg | Standard Deviation 1.1 |
| Ivacaftor 75 mg | Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Absolute Change at Week 72 (n=9, 20) | 3.3 Kg | Standard Deviation 1.4 |