Cystic Fibrosis
Conditions
Brief summary
This is a Phase 3, 2-part (Part A and Part B), open-label, multicenter study to evaluate the pharmacokinetics, safety, and tolerability of lumacaftor in combination with ivacaftor in subjects with cystic fibrosis aged 6 to 11 years who have the F508del-mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Interventions
DRUGLumacaftor
DRUGIvacaftor
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of CF defined as: with 2 CF-causing mutations, chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities * Subjects who weigh ≥15 kg without shoes at Screening Visit * Subjects who are homozygous for the F508del-CFTR mutation * Subjects with percent predicted forced expiratory volume in 1 second (FEV1) of 70% to 105% (inclusive) (Part A) or ≥40% (Part B) at Screening Visit where the predicted values are adjusted for age, sex, and height using the Wang equation * Subjects with stable CF disease and who are willing to remain on stable CF medication regimen * Able to swallow tablets
Exclusion criteria
* History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject * Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1 of the study * Abnormal liver function as defined in the protocol at Screening Visit * Abnormal renal function as defined in the protocol at Screening Visit * History of solid organ or hematological transplantation * Ongoing participation in an investigational drug study or prior participation in an investigational drug study within 30 days prior of Screening Visit * History or evidence of lens opacity or cataract at Screening Visit * Colonization with organisms associated with a more rapid decline in pulmonary status at Screening Visit (Part A only) * A standard 12-lead ECG demonstrating QTcF \>450 msec at Screening Visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1 | 4 hours post-morning dose on Day 1 | — |
| Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 14 | 4 hours post-morning dose on Day 14 | — |
| Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to End of Dosing Interval (AUCtau) of Lumacaftor (LUM) and Ivacaftor (IVA) | Day 14 (pre-morning dose, 4, 6, 12, and 24 hours post-morning dose for LUM; pre-morning dose, 2, 4, 6, 12 hours post-morning dose for IVA) | The AUCtau is the area under the concentration versus time curve from time 0 to time tau, where tau is the time at the end of dosing interval. |
| Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Week 26 | 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 study drug dose to Week 26 were considered treatment-emergent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | Baseline, Week 24 | BMI was defined as weight in kilogram (kg) divided by height\*height in square meter (m\^2). |
| Part B: Absolute Change From Baseline in BMI-for-age Z-score at Week 24 | Baseline, Week 24 | BMI was defined as weight in kg divided by height\*height in m\^2. z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is, with range from -infinity to +infinity; where 0: same mean, \>0: a greater mean, and \<0: a lesser mean than the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score). The BMI-for-age z-scores were calculated using National Center for Health Statistics growth charts. |
| Part B: Absolute Change From Baseline in Weight at Week 24 | Baseline, Week 24 | — |
| Part B: Absolute Change From Baseline in Weight-for-age Z-score at Week 24 | Baseline, Week 24 | Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is, with range from -infinity to +infinity; where 0: same mean, \>0: a greater mean, and \<0: a lesser mean than the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score (weight z-score). The weight-for-age z-scores were calculated using National Center for Health Statistics growth charts. |
| Part A: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14 | Day 1, Day 14 | — |
| Part B: Absolute Change From Baseline in Height-for-age Z-score at Week 24 | Baseline, Week 24 | Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is, with range from -infinity to +infinity; where 0: same mean, \>0: a greater mean, and \<0: a lesser mean than the standard. Height, adjusted for age and sex, was analyzed as height-for-age z-score (height z-score). The height-for-age z-scores were calculated using National Center for Health Statistics growth charts. |
| Part B: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24 | Baseline, Week 24 | The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. |
| Part B: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains at Week 24 | Baseline, Week 24 | The TSQM is a 14-item self-administered questionnaire which measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed to a scale from 0 to 100, where higher scores indicate greater satisfaction. |
| Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | For Ctrough: pre-morning dose on Week 4, Week 6 and Week 24; For C3-6hr: 3 to 6 hours post-morning dose on Day 1, 15 and Week 4 | Ctrough and C3-6hr for lumacaftor, M28 lumacaftor (lumacaftor metabolite), ivacaftor, M1 ivacaftor (ivacaftor metabolite), and M6 ivacaftor (ivacaftor metabolite) were calculated. Ctrough was observed pre-dose concentration. C3-6hr was observed concentration at 3 to 6 hours post- dose. |
| Part B: Absolute Change From Baseline in Height at Week 24 | Baseline, Week 24 | — |
| Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Day 28 | 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 study drug dose through the end of Part A were considered treatment-emergent. |
| Part B: Average Absolute Change From Baseline in Sweat Chloride at Day 15 and at Week 4 | Baseline, Day 15 and Week 4 | Sweat samples were collected using an approved collection device. Baseline was defined as the average of the measurements at screening and on Day 1 pre-dose. Average of Day 15 and Week 4 measurements was taken and change was calculated as: Average (Day 15 and Week 4 measurement) minus Baseline measurement. |
| Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26 | Week 24, Week 26 | Sweat samples were collected using an approved collection device. Change = Week 26 minus Week 24. |
Countries
Canada, United States
Participant flow
Pre-assignment details
The study was conducted in 2 parts - Part A and Part B. Part A consisted of 2 cohorts, in which participants aged 6 to 8 years were enrolled in Cohort 1 and participants aged 9 to 11 years were enrolled in Cohort 2. Part B consisted of a single cohort. Participants from Part A may have also participated in Part B of the study.
Participants by arm
| Arm | Count |
|---|---|
| Lumacaftor/Ivacaftor (LUM/IVA) Part A Cohort 1: Participants aged 6 through 8 years received LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 14 days.
Part A Cohort 2: Participants aged 9 through 11 years received LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 14 days.
Part B: Participants aged 6 through 11 years received LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 24 weeks. | 62 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Part B (24 Weeks) | Adverse Event | 1 |
| Part B (24 Weeks) | Physician Decision | 1 |
| Part B (24 Weeks) | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Lumacaftor/Ivacaftor (LUM/IVA) |
|---|---|
| Age, Continuous Part A Cohort 1 (n=5) | 6.6 years STANDARD_DEVIATION 0.89 |
| Age, Continuous Part A Cohort 2 (n=5) | 9.6 years STANDARD_DEVIATION 0.89 |
| Age, Continuous Part B (n=58) | 9.1 years STANDARD_DEVIATION 1.53 |
| Sex/Gender, Customized Part A Cohort 1 (n=5): Female | 1 participants |
| Sex/Gender, Customized Part A Cohort 1 (n=5): Male | 4 participants |
| Sex/Gender, Customized Part A Cohort 2 (n=5): Female | 1 participants |
| Sex/Gender, Customized Part A Cohort 2 (n=5): Male | 4 participants |
| Sex/Gender, Customized Part B (n=58): Female | 31 participants |
| Sex/Gender, Customized Part B (n=58): Male | 27 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 | 4 / 5 | 3 / 5 | 55 / 58 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 4 / 58 |
Outcome results
Primary
Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to End of Dosing Interval (AUCtau) of Lumacaftor (LUM) and Ivacaftor (IVA)
The AUCtau is the area under the concentration versus time curve from time 0 to time tau, where tau is the time at the end of dosing interval.
Time frame: Day 14 (pre-morning dose, 4, 6, 12, and 24 hours post-morning dose for LUM; pre-morning dose, 2, 4, 6, 12 hours post-morning dose for IVA)
Population: The PK Set included all enrolled participants who received the study drug and for whom the primary PK data were considered to be sufficient and interpretable.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A Overall Arm: LUM/IVA | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to End of Dosing Interval (AUCtau) of Lumacaftor (LUM) and Ivacaftor (IVA) | LUM | 387600 ng*hr/mL |
| Part A Overall Arm: LUM/IVA | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to End of Dosing Interval (AUCtau) of Lumacaftor (LUM) and Ivacaftor (IVA) | IVA | 6838 ng*hr/mL |
Primary
Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1
Time frame: 4 hours post-morning dose on Day 1
Population: The Pharmacokinetic (PK) Set included all enrolled participants who received the study drug and for whom the primary PK data were considered to be sufficient and interpretable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Overall Arm: LUM/IVA | Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1 | LUM | 15200 nanogram per milliliter (ng/mL) | Standard Deviation 6740 |
| Part A Overall Arm: LUM/IVA | Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1 | IVA | 1920 nanogram per milliliter (ng/mL) | Standard Deviation 727 |
Primary
Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 14
Time frame: 4 hours post-morning dose on Day 14
Population: The PK Set included all enrolled participants who received the study drug and for whom the primary PK data were considered to be sufficient and interpretable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Overall Arm: LUM/IVA | Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 14 | LUM | 24500 ng/mL | Standard Deviation 10400 |
| Part A Overall Arm: LUM/IVA | Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 14 | IVA | 622 ng/mL | Standard Deviation 322 |
Primary
Part B: 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 study drug dose to Week 26 were considered treatment-emergent.
Time frame: Day 1 up to Week 26
Population: The Safety Set included all participants who received any amount of Part B study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A Overall Arm: LUM/IVA | Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 55 participants |
| Part A Overall Arm: LUM/IVA | Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 4 participants |
Secondary
Part A: 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 study drug dose through the end of Part A were considered treatment-emergent.
Time frame: Day 1 up to Day 28
Population: The Safety Set included all participants who received at least 1 dose of study drug. Here n signifies those subjects who were evaluable for the specified cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A Overall Arm: LUM/IVA | Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Part A Cohort 1: AEs (n=5) | 4 participants |
| Part A Overall Arm: LUM/IVA | Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Part A Cohort 1: SAEs (n=5) | 0 participants |
| Part A Overall Arm: LUM/IVA | Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Part A Cohort 2: AEs (n=5) | 3 participants |
| Part A Overall Arm: LUM/IVA | Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Part A Cohort 2: SAEs (n=5) | 0 participants |
Secondary
Part A: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14
Time frame: Day 1, Day 14
Population: The PK Set included all enrolled participants who received the study drug and for whom the primary PK data were considered to be sufficient and interpretable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Overall Arm: LUM/IVA | Part A: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14 | M28-LUM (Day 1) | 176 ng/mL | Standard Deviation 79 |
| Part A Overall Arm: LUM/IVA | Part A: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14 | M1-IVA (Day 1) | 3940 ng/mL | Standard Deviation 1380 |
| Part A Overall Arm: LUM/IVA | Part A: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14 | M6-IVA (Day 1) | 1810 ng/mL | Standard Deviation 981 |
| Part A Overall Arm: LUM/IVA | Part A: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14 | M28-LUM (Day 14) | 2040 ng/mL | Standard Deviation 1230 |
| Part A Overall Arm: LUM/IVA | Part A: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14 | M1-IVA (Day 14) | 2380 ng/mL | Standard Deviation 1360 |
| Part A Overall Arm: LUM/IVA | Part A: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14 | M6-IVA (Day 14) | 4240 ng/mL | Standard Deviation 1990 |
Secondary
Part B: Absolute Change From Baseline in BMI-for-age Z-score at Week 24
BMI was defined as weight in kg divided by height\*height in m\^2. z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is, with range from -infinity to +infinity; where 0: same mean, \>0: a greater mean, and \<0: a lesser mean than the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score). The BMI-for-age z-scores were calculated using National Center for Health Statistics growth charts.
Time frame: Baseline, Week 24
Population: The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A Overall Arm: LUM/IVA | Part B: Absolute Change From Baseline in BMI-for-age Z-score at Week 24 | 0.15 z-score |
Secondary
Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
BMI was defined as weight in kilogram (kg) divided by height\*height in square meter (m\^2).
Time frame: Baseline, Week 24
Population: The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A Overall Arm: LUM/IVA | Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | 0.64 kilogram per square meter (kg/m^2) |
Secondary
Part B: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24
The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time frame: Baseline, Week 24
Population: The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A Overall Arm: LUM/IVA | Part B: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24 | 5.4 Units on a scale |
Secondary
Part B: Absolute Change From Baseline in Height at Week 24
Time frame: Baseline, Week 24
Population: The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A Overall Arm: LUM/IVA | Part B: Absolute Change From Baseline in Height at Week 24 | 2.9 centimeter (cm) |
Secondary
Part B: Absolute Change From Baseline in Height-for-age Z-score at Week 24
Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is, with range from -infinity to +infinity; where 0: same mean, \>0: a greater mean, and \<0: a lesser mean than the standard. Height, adjusted for age and sex, was analyzed as height-for-age z-score (height z-score). The height-for-age z-scores were calculated using National Center for Health Statistics growth charts.
Time frame: Baseline, Week 24
Population: The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A Overall Arm: LUM/IVA | Part B: Absolute Change From Baseline in Height-for-age Z-score at Week 24 | 0.03 z-score |
Secondary
Part B: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains at Week 24
The TSQM is a 14-item self-administered questionnaire which measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed to a scale from 0 to 100, where higher scores indicate greater satisfaction.
Time frame: Baseline, Week 24
Population: The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A Overall Arm: LUM/IVA | Part B: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains at Week 24 | Change at Week 24: Effectiveness | 9.2 units on a scale |
| Part A Overall Arm: LUM/IVA | Part B: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains at Week 24 | Change at Week 24: Side Effects | -0.3 units on a scale |
| Part A Overall Arm: LUM/IVA | Part B: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains at Week 24 | Change at Week 24: Convenience | 11.1 units on a scale |
| Part A Overall Arm: LUM/IVA | Part B: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains at Week 24 | Change at Week 24: Global Score | 3.6 units on a scale |
Secondary
Part B: Absolute Change From Baseline in Weight at Week 24
Time frame: Baseline, Week 24
Population: The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A Overall Arm: LUM/IVA | Part B: Absolute Change From Baseline in Weight at Week 24 | 2.6 kilograms (kg) |
Secondary
Part B: Absolute Change From Baseline in Weight-for-age Z-score at Week 24
Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is, with range from -infinity to +infinity; where 0: same mean, \>0: a greater mean, and \<0: a lesser mean than the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score (weight z-score). The weight-for-age z-scores were calculated using National Center for Health Statistics growth charts.
Time frame: Baseline, Week 24
Population: The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A Overall Arm: LUM/IVA | Part B: Absolute Change From Baseline in Weight-for-age Z-score at Week 24 | 0.13 z-score |
Secondary
Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26
Sweat samples were collected using an approved collection device. Change = Week 26 minus Week 24.
Time frame: Week 24, Week 26
Population: The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A Overall Arm: LUM/IVA | Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26 | 21.3 mmol/L |
Secondary
Part B: Average Absolute Change From Baseline in Sweat Chloride at Day 15 and at Week 4
Sweat samples were collected using an approved collection device. Baseline was defined as the average of the measurements at screening and on Day 1 pre-dose. Average of Day 15 and Week 4 measurements was taken and change was calculated as: Average (Day 15 and Week 4 measurement) minus Baseline measurement.
Time frame: Baseline, Day 15 and Week 4
Population: The Full Analysis Set (FAS) included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A Overall Arm: LUM/IVA | Part B: Average Absolute Change From Baseline in Sweat Chloride at Day 15 and at Week 4 | -19.7 millimole per liter (mmol/L) |
Secondary
Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA)
Ctrough and C3-6hr for lumacaftor, M28 lumacaftor (lumacaftor metabolite), ivacaftor, M1 ivacaftor (ivacaftor metabolite), and M6 ivacaftor (ivacaftor metabolite) were calculated. Ctrough was observed pre-dose concentration. C3-6hr was observed concentration at 3 to 6 hours post- dose.
Time frame: For Ctrough: pre-morning dose on Week 4, Week 6 and Week 24; For C3-6hr: 3 to 6 hours post-morning dose on Day 1, 15 and Week 4
Population: The PK Set included all enrolled participants who received the study drug and for whom the primary PK data were considered to be sufficient and interpretable. Here n signifies those participants who were evaluable at the specified time point for the given category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h LUM (Day 15) (n=55) | 21400 ng/mL | Standard Deviation 6850 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h IVA (Day 15) (n=55) | 751 ng/mL | Standard Deviation 433 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h M28-LUM (Day 15) (n=55) | 1660 ng/mL | Standard Deviation 843 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h M1-IVA (Day 15) (n=55) | 2670 ng/mL | Standard Deviation 1330 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h M6-IVA (Week 4) (n=54) | 4690 ng/mL | Standard Deviation 3360 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough LUM (Week 4) (n=53) | 12300 ng/mL | Standard Deviation 6780 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough IVA (Week 4) (n=53) | 171 ng/mL | Standard Deviation 228 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough M28-LUM (Week 4) (n=53) | 1780 ng/mL | Standard Deviation 903 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough M1-IVA (Week 4) (n=53) | 684 ng/mL | Standard Deviation 816 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough M6-IVA (Week 4) (n=53) | 2490 ng/mL | Standard Deviation 2150 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough LUM (Week 16) (n=53) | 11500 ng/mL | Standard Deviation 6020 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough IVA (Week 16) (n=52) | 153 ng/mL | Standard Deviation 150 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough M28-LUM (Week 16) (n=53) | 1610 ng/mL | Standard Deviation 859 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough M1-IVA (Week 16) (n=53) | 690 ng/mL | Standard Deviation 627 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough M6-IVA (Week 16) (n=53) | 2360 ng/mL | Standard Deviation 1570 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough LUM (Week 24) (n=51) | 11400 ng/mL | Standard Deviation 5300 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h LUM (Day 1) (n=57) | 17100 ng/mL | Standard Deviation 6260 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h IVA (Day 1) (n=57) | 1980 ng/mL | Standard Deviation 850 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h M28-LUM (Day 1) (n=57) | 186 ng/mL | Standard Deviation 96.3 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h M1-IVA (Day 1) (n=57) | 4170 ng/mL | Standard Deviation 1940 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h M6-IVA (Day 1) (n=57) | 2040 ng/mL | Standard Deviation 1650 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h M6-IVA (Day 15) (n=55) | 4360 ng/mL | Standard Deviation 2340 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h LUM (Week 4) (n=54) | 22000 ng/mL | Standard Deviation 8470 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h IVA (Week 4) (n=54) | 779 ng/mL | Standard Deviation 389 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h M28-LUM (Week 4) (n=54) | 1730 ng/mL | Standard Deviation 884 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | C3-6h M1-IVA (Week 4) (n=54) | 2800 ng/mL | Standard Deviation 1410 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough IVA (Week 24) (n=51) | 118 ng/mL | Standard Deviation 87.2 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough M28-LUM (Week 24) (n=51) | 1710 ng/mL | Standard Deviation 947 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough M1-IVA (Week 24) (n=51) | 493 ng/mL | Standard Deviation 409 |
| Part A Overall Arm: LUM/IVA | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough M6-IVA (Week 24) (n=51) | 1790 ng/mL | Standard Deviation 1180 |