Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis
Brief summary
The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD), of ivacaftor in children with cystic fibrosis (CF) who are 2 through 5 years of age and have a CF Transmembrane Conductance Regulator (CFTR) gating mutation in at least 1 allele. Part A is designed to evaluate the safety and PK of multiple-dose administration of ivacaftor in participants 2 through 5 years of age and to confirm the doses for Part B. Part B is designed to evaluate the safety, PK, PD, and efficacy of ivacaftor in participants 2 through 5 years of age.
Interventions
DRUGIvacaftor
Sponsors
Cystic Fibrosis Foundation
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
* Male or female with confirmed diagnosis of CF * Must have a CFTR gating mutation in at least 1 allele * Aged 2 through 5 years at screening and Day 1 * Weight \>= 8 kg at screening and Day 1 * Hematology, serum chemistry, coagulation, and vital signs results at screening with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator
Exclusion criteria
* History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant * An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks before Day 1 * Abnormal liver function, at screening * History of solid organ or hematological transplantation * Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1 * Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives before screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | Part A: Up to 93 Days | AE: any adverse change from participant'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. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants. |
| Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | Part B: Up to 28 Weeks | AE: any adverse change from participant'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. AE includes both serious and non-serious AE. 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. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received. |
| Part A: Plasma Concentration of Ivacaftor and Its Metabolites | Part A: up to 24 hours post-dose on Day 4 | Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor \[M1\] and ivacaftor carboxylate \[M6\]) up to 24 hours post-dose on Day 4 (Hour 0 \[pre-dose\] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Absolute Change From Baseline in Stature at Week 24 | Part B: Baseline, Week 24 | Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Data was reported as per the dose received and for overall participants. |
| Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Part B: up to 24 hours post-dose on Day 168 | Plasma concentration was reported for ivacaftor and its metabolites (M1 and M6) up to 24 hours post-dose on Day 168 (Hour 0 \[predose\] on Day 1, 14, 56, 112, and 168; 2, 3, 6 hours post-dose on Day 14; 1 hour post-dose on Day 56; 4, 6 hours post-dose on Day 112; 24 hours post-dose on Day 168). Data was planned to be reported for overall participants in the period. |
| Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | Baseline, Week 24 | BMI = (Weight \[in kg\]) divided by (Stature \[in meters\])\^2. Data was reported as per the dose received and for overall participants. |
| Part B: Absolute Change From Baseline in Sweat Chloride at Week 24 | Part B: Baseline, Week 24 | 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. Data was reported as per the dose received and for overall participants. |
| Part B: Absolute Change From Baseline in Weight at Week 24 | Part B: Baseline, Week 24 | Data was reported as per the dose received and for overall participants. |
Countries
Canada, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ivacaftor Part A: Ivacaftor 50 mg (for participants weighing \<14 kg) or 75 mg (for participants weighing \>=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.
Part B: Ivacaftor 50 mg (for participants weighing \<14 kg) or 75 mg (for participants weighing \>=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Part B | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Ivacaftor |
|---|---|
| Age, Continuous Part A (n = 9) | 3.1 years STANDARD_DEVIATION 1.17 |
| Age, Continuous Part B (n = 34) | 3.2 years STANDARD_DEVIATION 0.96 |
| Sex/Gender, Customized Part A (n = 9): Female | 3 participants |
| Sex/Gender, Customized Part A (n = 9): Male | 6 participants |
| Sex/Gender, Customized Part B (n = 34): Female | 6 participants |
| Sex/Gender, Customized Part B (n = 34): Male | 28 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 4 | 5 / 5 | 8 / 9 | 9 / 10 | 23 / 24 | 32 / 34 |
| serious Total, serious adverse events | 0 / 4 | 0 / 5 | 0 / 9 | 3 / 10 | 3 / 24 | 6 / 34 |
Outcome results
Primary
Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
AE: any adverse change from participant'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. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.
Time frame: Part A: Up to 93 Days
Population: Part A Safety set included all participants who received at least 1 dose of study drug in part A.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Ivacaftor 50 mg | Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | SAEs | 0 participants |
| Part A: Ivacaftor 50 mg | Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | AEs | 3 participants |
| Part A: Ivacaftor 50 mg | Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | Related AEs | 1 participants |
| Part A: Ivacaftor 75 mg | Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | SAEs | 0 participants |
| Part A: Ivacaftor 75 mg | Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | AEs | 5 participants |
| Part A: Ivacaftor 75 mg | Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | Related AEs | 3 participants |
| Part A: Overall Ivacaftor | Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | AEs | 8 participants |
| Part A: Overall Ivacaftor | Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | Related AEs | 4 participants |
| Part A: Overall Ivacaftor | Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | SAEs | 0 participants |
Primary
Part A: Plasma Concentration of Ivacaftor and Its Metabolites
Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor \[M1\] and ivacaftor carboxylate \[M6\]) up to 24 hours post-dose on Day 4 (Hour 0 \[pre-dose\] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.
Time frame: Part A: up to 24 hours post-dose on Day 4
Population: Part A Safety set included all participants who received at least 1 dose of study drug in part A.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: Hour 0 on Day 1 | 0.00 nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: Hour 0 on Day 4 | 396 nanogram per milliliter (ng/mL) | Standard Deviation 337 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: 2 Hours Post-Dose on Day 4 | 726 nanogram per milliliter (ng/mL) | Standard Deviation 284 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: 3 Hours Post-Dose on Day 4 | 957 nanogram per milliliter (ng/mL) | Standard Deviation 283 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: 6 Hours Post-Dose on Day 4 | 542 nanogram per milliliter (ng/mL) | Standard Deviation 241 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: 24 Hours Post-Dose on Day 4 | 124 nanogram per milliliter (ng/mL) | Standard Deviation 149 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | M1: Hour 0 on Day 1 | 0.00 nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | M1: Hour 0 on Day 4 | 1240 nanogram per milliliter (ng/mL) | Standard Deviation 723 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | M1: 2 Hours Post-Dose on Day 4 | 1540 nanogram per milliliter (ng/mL) | Standard Deviation 578 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | M1: 3 Hours Post-Dose on Day 4 | 2310 nanogram per milliliter (ng/mL) | Standard Deviation 820 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | M1: 6 Hours Post-Dose on Day 4 | 1580 nanogram per milliliter (ng/mL) | Standard Deviation 622 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | M1: 24 Hours Post-Dose on Day 4 | 389 nanogram per milliliter (ng/mL) | Standard Deviation 336 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | M6: Hour 0 on Day 1 | 0.00 nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | M6: Hour 0 on Day 4 | 1150 nanogram per milliliter (ng/mL) | Standard Deviation 709 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | M6: 2 Hours Post-Dose on Day 4 | 1050 nanogram per milliliter (ng/mL) | Standard Deviation 606 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | M6: 3 Hours Post-Dose on Day 4 | 1300 nanogram per milliliter (ng/mL) | Standard Deviation 614 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | M6: 6 Hours Post-Dose on Day 4 | 1390 nanogram per milliliter (ng/mL) | Standard Deviation 532 |
| Part A: Ivacaftor 50 mg | Part A: Plasma Concentration of Ivacaftor and Its Metabolites | M6: 24 Hours Post-Dose on Day 4 | 439 nanogram per milliliter (ng/mL) | Standard Deviation 355 |
Primary
Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
AE: any adverse change from participant'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. AE includes both serious and non-serious AE. 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. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.
Time frame: Part B: Up to 28 Weeks
Population: Part B Safety set included all participants who received at least 1 dose of study drug in part B.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Ivacaftor 50 mg | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | SAEs | 3 participants |
| Part A: Ivacaftor 50 mg | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | AEs | 10 participants |
| Part A: Ivacaftor 50 mg | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | Related AEs | 3 participants |
| Part A: Ivacaftor 75 mg | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | SAEs | 3 participants |
| Part A: Ivacaftor 75 mg | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | AEs | 23 participants |
| Part A: Ivacaftor 75 mg | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | Related AEs | 8 participants |
| Part A: Overall Ivacaftor | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | AEs | 33 participants |
| Part A: Overall Ivacaftor | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | Related AEs | 11 participants |
| Part A: Overall Ivacaftor | Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs | SAEs | 6 participants |
Secondary
Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
BMI = (Weight \[in kg\]) divided by (Stature \[in meters\])\^2. Data was reported as per the dose received and for overall participants.
Time frame: Baseline, Week 24
Population: Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Ivacaftor 50 mg | Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | 0.332 kilogram per square meter (kg/m^2) | Standard Deviation 0.5393 |
| Part A: Ivacaftor 75 mg | Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | 0.314 kilogram per square meter (kg/m^2) | Standard Deviation 0.5492 |
| Part A: Overall Ivacaftor | Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | 0.319 kilogram per square meter (kg/m^2) | Standard Deviation 0.5378 |
Secondary
Part B: Absolute Change From Baseline in Stature at Week 24
Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Data was reported as per the dose received and for overall participants.
Time frame: Part B: Baseline, Week 24
Population: Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Ivacaftor 50 mg | Part B: Absolute Change From Baseline in Stature at Week 24 | 2.5 centimeters (cm) | Standard Deviation 1.45 |
| Part A: Ivacaftor 75 mg | Part B: Absolute Change From Baseline in Stature at Week 24 | 3.5 centimeters (cm) | Standard Deviation 0.93 |
| Part A: Overall Ivacaftor | Part B: Absolute Change From Baseline in Stature at Week 24 | 3.3 centimeters (cm) | Standard Deviation 1.17 |
Secondary
Part B: Absolute Change From Baseline in Sweat Chloride at Week 24
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. Data was reported as per the dose received and for overall participants.
Time frame: Part B: Baseline, Week 24
Population: Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Ivacaftor 50 mg | Part B: Absolute Change From Baseline in Sweat Chloride at Week 24 | -47.07 millimole per liter (mmol/L) | Standard Deviation 24.256 |
| Part A: Ivacaftor 75 mg | Part B: Absolute Change From Baseline in Sweat Chloride at Week 24 | -46.78 millimole per liter (mmol/L) | Standard Deviation 27.584 |
| Part A: Overall Ivacaftor | Part B: Absolute Change From Baseline in Sweat Chloride at Week 24 | -46.86 millimole per liter (mmol/L) | Standard Deviation 26.193 |
Secondary
Part B: Absolute Change From Baseline in Weight at Week 24
Data was reported as per the dose received and for overall participants.
Time frame: Part B: Baseline, Week 24
Population: Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Ivacaftor 50 mg | Part B: Absolute Change From Baseline in Weight at Week 24 | 1.00 kilograms (kg) | Standard Deviation 0.418 |
| Part A: Ivacaftor 75 mg | Part B: Absolute Change From Baseline in Weight at Week 24 | 1.50 kilograms (kg) | Standard Deviation 0.552 |
| Part A: Overall Ivacaftor | Part B: Absolute Change From Baseline in Weight at Week 24 | 1.36 kilograms (kg) | Standard Deviation 0.561 |
Secondary
Part B: Plasma Concentration of Ivacaftor and Its Metabolites
Plasma concentration was reported for ivacaftor and its metabolites (M1 and M6) up to 24 hours post-dose on Day 168 (Hour 0 \[predose\] on Day 1, 14, 56, 112, and 168; 2, 3, 6 hours post-dose on Day 14; 1 hour post-dose on Day 56; 4, 6 hours post-dose on Day 112; 24 hours post-dose on Day 168). Data was planned to be reported for overall participants in the period.
Time frame: Part B: up to 24 hours post-dose on Day 168
Population: Part B Safety set included all participants who received at least 1 dose of study drug in part B.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M1: Hour 0 on Day 112 | 1680 ng/mL | Standard Deviation 1360 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: Hour 0 on Day 1 | 0.00 ng/mL | Standard Deviation 0 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: Hour 0 on Day 14 | 614 ng/mL | Standard Deviation 590 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: 2 Hours Post-Dose on Day 14 | 932 ng/mL | Standard Deviation 541 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: 3 Hours Post-Dose on Day 14 | 1080 ng/mL | Standard Deviation 587 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: 6 Hours Post-Dose on Day 14 | 1140 ng/mL | Standard Deviation 627 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: Hour 0 on Day 56 | 448 ng/mL | Standard Deviation 455 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: 1 Hour Post-Dose on Day 56 | 514 ng/mL | Standard Deviation 421 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: Hour 0 on Day 112 | 596 ng/mL | Standard Deviation 747 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: 4 Hours Post-Dose on Day 112 | 1080 ng/mL | Standard Deviation 835 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: 6 Hours Post-Dose on Day 112 | 1010 ng/mL | Standard Deviation 885 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: Hour 0 on Day 168 | 500 ng/mL | Standard Deviation 545 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | Ivacaftor: 24 Hours Post-Dose on Day 168 | 207 ng/mL | Standard Deviation 372 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M1: Hour 0 on Day 14 | 1580 ng/mL | Standard Deviation 1030 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M1: 2 Hours Post-Dose on Day 14 | 1870 ng/mL | Standard Deviation 924 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M1: 3 Hours Post-Dose on Day 14 | 2280 ng/mL | Standard Deviation 1140 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M1: 6 Hours Post-Dose on Day 14 | 2670 ng/mL | Standard Deviation 1080 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M1: Hour 0 on Day 56 | 1340 ng/mL | Standard Deviation 880 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M1: 1 Hour Post-Dose on Day 56 | 1170 ng/mL | Standard Deviation 698 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M1: 4 Hours Post-Dose on Day 112 | 2450 ng/mL | Standard Deviation 1510 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M1: 6 Hours Post-Dose on Day 112 | 2500 ng/mL | Standard Deviation 1520 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M1: Hour 0 on Day 168 | 1460 ng/mL | Standard Deviation 1200 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M1: 24 Hours Post-Dose on Day 168 | 602 ng/mL | Standard Deviation 647 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M6: Hour 0 on Day 1 | 0.00 ng/mL | Standard Deviation 0 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M6: Hour 0 on Day 14 | 1520 ng/mL | Standard Deviation 1130 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M6: 2 Hours Post-Dose on Day 14 | 1430 ng/mL | Standard Deviation 989 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M6: 3 Hours Post-Dose on Day 14 | 1630 ng/mL | Standard Deviation 1130 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M6: 6 Hours Post-Dose on Day 14 | 2090 ng/mL | Standard Deviation 1350 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M6: Hour 0 on Day 56 | 1510 ng/mL | Standard Deviation 1080 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M6: 1 Hour Post-Dose on Day 56 | 1310 ng/mL | Standard Deviation 974 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M6: Hour 0 on Day 112 | 1660 ng/mL | Standard Deviation 1130 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M6: 4 Hours Post-Dose on Day 112 | 1810 ng/mL | Standard Deviation 1230 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M6: 6 Hours Post-Dose on Day 112 | 2130 ng/mL | Standard Deviation 1380 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M6: Hour 0 on Day 168 | 1520 ng/mL | Standard Deviation 1130 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M6: 24 Hours Post-Dose on Day 168 | 632 ng/mL | Standard Deviation 465 |
| Part A: Ivacaftor 50 mg | Part B: Plasma Concentration of Ivacaftor and Its Metabolites | M1: Hour 0 on Day 1 | 0.00 ng/mL | Standard Deviation 0 |