Cystic Fibrosis
Conditions
Keywords
CF
Brief summary
This is a Phase 3, 2-part (Part A and Part B), open-label, multicenter study evaluating the pharmacokinetics (PK), safety, tolerability, and pharmacodynamics (PD) of multiple doses of lumacaftor/ivacaftor (LUM/IVA) in subjects 2 through 5 years of age (inclusive) with cystic fibrosis (CF), homozygous for F508del. Subjects who participate in Part A may participate in Part B, if they meet the eligibility criteria.
Interventions
DRUGLUM/IVA
Sponsors
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
* Subjects who weigh ≥8 kilogram (kg) without shoes and wearing light clothing at the Screening Visit * Subjects with confirmed diagnosis of CF at the Screening Visit * Subjects who are homozygous for the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) mutation
Exclusion criteria
* Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject * An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 * A standard 12-lead ECG demonstrating QTc \>450 millisecond (msec) at the Screening Visit. * History of solid organ or hematological transplantation. * Ongoing or prior participation in an investigational drug study (including studies investigating LUM and/or IVA) within 30 days of the Screening Visit. * History of cataract/lens opacity or evidence of cataract/lens opacity determined to be clinically significant by a licensed ophthalmologist during the ophthalmologic examination at the Screening Visit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Pre-dose Concentration (Ctrough) of LUM and IVA | Day 15 |
| Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Week 26 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Absolute Change From Baseline in Sweat Chloride at Week 24 | Baseline, Week 24 | Sweat samples were collected using an approved collection device. |
| Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | Baseline, Week 24 | BMI was defined as weight in kilograms (kg) divided by height in square meter (m\^2). |
| Part B: Absolute Change From Baseline in Body Mass Index (BMI) For-Age Z-Score at Week 24 | Baseline, Week 24 | BMI was defined as weight in kg divided by height in m\^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score). |
| 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 describe whether a mean was above or below the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score (Weight z-score). |
| Part B: Absolute Change From Baseline in Stature (Height) at Week 24 | Baseline, Week 24 | — |
| Part B: Absolute Change From Baseline in Stature-for-Age Z-Score | Baseline, Week 24 | z-score is a statistical measure to describe whether a mean was above or below the standard. Stature (height), adjusted for age and sex, was analyzed as Stature-for-age z-score (Stature z-score). |
| Part B: Number of Pulmonary Exacerbations | Through Week 24 | Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. |
| Part B: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24 | Through Week 24 | Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. Time to event data was not collected and instead, number of participants with first event were collected and are reported. Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates. However, due to less than 50% of events, time-to-first event data was not estimated. Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported. |
| Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites | Day 15 | — |
| Part B: Absolute Change From Baseline in Fecal Elastase-1 (FE-1) Levels at Week 24 | Baseline, Week 24 | — |
| Part B: Absolute Change From Baseline in Serum Levels of Immunoreactive Trypsinogen (IRT) Through Week 24 | Baseline, Through Week 24 | — |
| Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline and Week 24 | Following microbial tests were performed: Burkholderia, Methicillin Resistant Staphylococcus Aureus (MRSA), Methicillin Susceptible Staphylococcus Aureus (MSSA), Pseudomonas Aeruginosa Mucoid (P. Aeruginosa Mucoid), P. Aeruginosa Non-Mucoid, P. Aeruginosa Small Colony Variant and Stenotrophomonas Maltophilia. |
| Part B: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 | Baseline, Week 24 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| 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. |
| Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Day 1 | The acceptability and palatability of LUM/IVA granules was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). The assessment was conducted in 2 steps: assessment of approved food/liquid (Evaluation 1), and assessment of approved food/liquid with LUM/IVA granules (Evaluation 2). |
| Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 2.5 at Week 24 | Baseline, Week 24 | Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value. |
| Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 5.0 at Week 24 | Baseline, Week 24 | LCI is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value. |
| Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites | Week 24 | — |
| Part B: Number of Cystic Fibrosis (CF)-Related Hospitalizations | Through Week 24 | — |
| Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Day 25 | — |
Countries
Canada, United States
Participant flow
Recruitment details
The study was conducted in 2 parts, Part A and Part B. In Parts A and B, participants received doses of lumacaftor/ivacaftor (LUM/IVA) based on weight. Participants from Part A may have also participated in Part B.
Participants by arm
| Arm | Count |
|---|---|
| Lumacaftor/Ivacaftor (LUM/IVA) Part A (\<14 kg): Participants weighing \<14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 15 days in Part A.
Part A (\>=14 kg): Participants weighing \>=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 15 days in Part A.
Part B (\<14 kg): Participants weighing \<14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Part B (\>=14 kg): Participants weighing \>=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B. | 62 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Part A (15 Days) | Adverse Event | 1 |
| Part B (24 Weeks) | Adverse Event | 3 |
Baseline characteristics
| Characteristic | Lumacaftor/Ivacaftor (LUM/IVA) |
|---|---|
| Age, Continuous Part A (<14 kg Weight) | 27.0 months STANDARD_DEVIATION 6 |
| Age, Continuous Part A (>=14 kg Weight) | 48.0 months STANDARD_DEVIATION 11.11 |
| Age, Continuous Part B (<14 kg Weight) | 31.6 months STANDARD_DEVIATION 5.05 |
| Age, Continuous Part B (>=14 kg Weight) | 49.9 months STANDARD_DEVIATION 10.63 |
| Ethnicity (NIH/OMB) Part A (<14 kg Weight) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Part A (<14 kg Weight) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Part A (<14 kg Weight) Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) Part A (>=14 kg Weight) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Part A (>=14 kg Weight) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Part A (>=14 kg Weight) Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) Part B (<14 kg Weight) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Part B (<14 kg Weight) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Part B (<14 kg Weight) Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) Part B (>=14 kg Weight) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Part B (>=14 kg Weight) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Part B (>=14 kg Weight) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Part A (<14 kg Weight) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Part A (<14 kg Weight) Asian | 0 Participants |
| Race (NIH/OMB) Part A (<14 kg Weight) Black or African American | 0 Participants |
| Race (NIH/OMB) Part A (<14 kg Weight) More than one race | 0 Participants |
| Race (NIH/OMB) Part A (<14 kg Weight) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Part A (<14 kg Weight) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Part A (<14 kg Weight) White | 4 Participants |
| Race (NIH/OMB) Part A (>=14 kg Weight) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Part A (>=14 kg Weight) Asian | 0 Participants |
| Race (NIH/OMB) Part A (>=14 kg Weight) Black or African American | 0 Participants |
| Race (NIH/OMB) Part A (>=14 kg Weight) More than one race | 0 Participants |
| Race (NIH/OMB) Part A (>=14 kg Weight) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Part A (>=14 kg Weight) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Part A (>=14 kg Weight) White | 8 Participants |
| Race (NIH/OMB) Part B (<14 kg Weight) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Part B (<14 kg Weight) Asian | 0 Participants |
| Race (NIH/OMB) Part B (<14 kg Weight) Black or African American | 0 Participants |
| Race (NIH/OMB) Part B (<14 kg Weight) More than one race | 0 Participants |
| Race (NIH/OMB) Part B (<14 kg Weight) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Part B (<14 kg Weight) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) Part B (<14 kg Weight) White | 18 Participants |
| Race (NIH/OMB) Part B (>=14 kg Weight) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Part B (>=14 kg Weight) Asian | 0 Participants |
| Race (NIH/OMB) Part B (>=14 kg Weight) Black or African American | 0 Participants |
| Race (NIH/OMB) Part B (>=14 kg Weight) More than one race | 0 Participants |
| Race (NIH/OMB) Part B (>=14 kg Weight) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Part B (>=14 kg Weight) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Part B (>=14 kg Weight) White | 41 Participants |
| Sex: Female, Male Part A (<14 kg Weight) Female | 2 Participants |
| Sex: Female, Male Part A (<14 kg Weight) Male | 2 Participants |
| Sex: Female, Male Part A (>=14 kg Weight) Female | 2 Participants |
| Sex: Female, Male Part A (>=14 kg Weight) Male | 6 Participants |
| Sex: Female, Male Part B (<14 kg Weight) Female | 9 Participants |
| Sex: Female, Male Part B (<14 kg Weight) Male | 10 Participants |
| Sex: Female, Male Part B (>=14 kg Weight) Female | 20 Participants |
| Sex: Female, Male Part B (>=14 kg Weight) Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 8 | 0 / 19 | 0 / 41 |
| other Total, other adverse events | 4 / 4 | 6 / 8 | 19 / 19 | 40 / 41 |
| serious Total, serious adverse events | 0 / 4 | 0 / 8 | 2 / 19 | 2 / 41 |
Outcome results
Primary
Part A: Pre-dose Concentration (Ctrough) of LUM and IVA
Time frame: Day 15
Population: The pharmacokinetic (PK) set for Part A included all participants who received at least 1 dose of LUM/IVA in Part A.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part A: Pre-dose Concentration (Ctrough) of LUM and IVA | LUM | 8710 nanogram per milliliter (ng/mL) | Standard Deviation 3590 |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part A: Pre-dose Concentration (Ctrough) of LUM and IVA | IVA | 94.0 nanogram per milliliter (ng/mL) | Standard Deviation 67 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part A: Pre-dose Concentration (Ctrough) of LUM and IVA | LUM | 12300 nanogram per milliliter (ng/mL) | Standard Deviation 5960 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part A: Pre-dose Concentration (Ctrough) of LUM and IVA | IVA | 216 nanogram per milliliter (ng/mL) | Standard Deviation 185 |
Primary
Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 26
Population: The Safety Set included all participants who received at least 1 dose of LUM/IVA in Part B.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 19 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 40 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
Secondary
Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Day 25
Population: The Safety Set included all participants who received at least 1 dose of LUM/IVA in Part A.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 4 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Secondary
Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites
Time frame: Day 15
Population: The PK set for Part A included all participants who received at least 1 dose of LUM/IVA in Part A.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites | LUM Metabolite (M28 LUM) | 1310 ng/mL | Standard Deviation 590 |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites | IVA Metabolite (M1 IVA) | 475 ng/mL | Standard Deviation 384 |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites | IVA Metabolite (M6 IVA) | 1510 ng/mL | Standard Deviation 1130 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites | LUM Metabolite (M28 LUM) | 1370 ng/mL | Standard Deviation 286 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites | IVA Metabolite (M1 IVA) | 1240 ng/mL | Standard Deviation 1180 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites | IVA Metabolite (M6 IVA) | 3270 ng/mL | Standard Deviation 2100 |
Secondary
Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
BMI was defined as weight in kilograms (kg) divided by height in square meter (m\^2).
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | 0.22 Kilogram per meter square (kg/m^2) | Standard Deviation 0.78 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | 0.29 Kilogram per meter square (kg/m^2) | Standard Deviation 0.75 |
Secondary
Part B: Absolute Change From Baseline in Body Mass Index (BMI) For-Age Z-Score at Week 24
BMI was defined as weight in kg divided by height in m\^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score).
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Absolute Change From Baseline in Body Mass Index (BMI) For-Age Z-Score at Week 24 | 0.36 Z-score | Standard Deviation 0.67 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change From Baseline in Body Mass Index (BMI) For-Age Z-Score at Week 24 | 0.26 Z-score | Standard Deviation 0.53 |
Secondary
Part B: Absolute Change From Baseline in Fecal Elastase-1 (FE-1) Levels at Week 24
Time frame: Baseline, Week 24
Population: The FAS included all enrolled subjects in Part B who were exposed to any amount of LUM/IVA in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Absolute Change From Baseline in Fecal Elastase-1 (FE-1) Levels at Week 24 | 38.4 microgram per gram | Standard Deviation 76.1 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change From Baseline in Fecal Elastase-1 (FE-1) Levels at Week 24 | 60.0 microgram per gram | Standard Deviation 94 |
Secondary
Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 2.5 at Week 24
Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Time frame: Baseline, Week 24
Population: The LCI Substudy Set included all participants who had signed informed consent (and assent, if applicable) to the optional LCI Substudy in Part B and enrolled and dosed in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 2.5 at Week 24 | 0.27 ratio | Standard Deviation 0.48 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 2.5 at Week 24 | -0.76 ratio | Standard Deviation 1.19 |
Secondary
Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 5.0 at Week 24
LCI is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.
Time frame: Baseline, Week 24
Population: The LCI Substudy Set included all subjects who had signed informed consent (and assent, if applicable) to the optional LCI Substudy in Part B and enrolled and dosed in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 5.0 at Week 24 | 0.24 ratio | Standard Deviation 0.4 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 5.0 at Week 24 | -0.12 ratio | Standard Deviation 0.69 |
Secondary
Part B: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: Baseline, Week 24
Population: Analysis population: participants \>=3 years of age with data available for Baseline and Week 24. Only participants from Part B (\>=14 Kg Weight) arm met the eligibility criteria for the specified time point and were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 | 0.5 percentage of predicted FEV1 | Standard Deviation 11.6 |
Secondary
Part B: Absolute Change From Baseline in Serum Levels of Immunoreactive Trypsinogen (IRT) Through Week 24
Time frame: Baseline, Through Week 24
Population: The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Absolute Change From Baseline in Serum Levels of Immunoreactive Trypsinogen (IRT) Through Week 24 | -262.1 ng/mL | Standard Deviation 343.1 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change From Baseline in Serum Levels of Immunoreactive Trypsinogen (IRT) Through Week 24 | -71.1 ng/mL | Standard Deviation 120.5 |
Secondary
Part B: Absolute Change From Baseline in Stature-for-Age Z-Score
z-score is a statistical measure to describe whether a mean was above or below the standard. Stature (height), adjusted for age and sex, was analyzed as Stature-for-age z-score (Stature z-score).
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Absolute Change From Baseline in Stature-for-Age Z-Score | 0.19 Z-score | Standard Deviation 0.32 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change From Baseline in Stature-for-Age Z-Score | 0.04 Z-score | Standard Deviation 0.19 |
Secondary
Part B: Absolute Change From Baseline in Stature (Height) at Week 24
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Absolute Change From Baseline in Stature (Height) at Week 24 | 4.1 Centimeter (cm) | Standard Deviation 1.4 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change From Baseline in Stature (Height) at Week 24 | 3.4 Centimeter (cm) | Standard Deviation 1 |
Secondary
Part B: Absolute Change From Baseline in Sweat Chloride at Week 24
Sweat samples were collected using an approved collection device.
Time frame: Baseline, Week 24
Population: The Full Analysis Set (FAS) included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Absolute Change From Baseline in Sweat Chloride at Week 24 | -33.5 millimole per liter (mmol/L) | Standard Deviation 14.5 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change From Baseline in Sweat Chloride at Week 24 | -30.7 millimole per liter (mmol/L) | Standard Deviation 14 |
Secondary
Part B: Absolute Change From Baseline in Weight at Week 24
Time frame: Baseline, Week 24
Population: The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Absolute Change From Baseline in Weight at Week 24 | 1.4 Kilogram (kg) | Standard Deviation 0.7 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change From Baseline in Weight at Week 24 | 1.5 Kilogram (kg) | Standard Deviation 1 |
Secondary
Part B: Absolute Change From Baseline in Weight-for-age Z-Score at Week 24
z-score is a statistical measure to describe whether a mean was above or below the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score (Weight z-score).
Time frame: Baseline, Week 24
Population: The FAS included all enrolled subjects in Part B who were exposed to any amount of LUM/IVA in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Absolute Change From Baseline in Weight-for-age Z-Score at Week 24 | 0.44 Z-score | Standard Deviation 0.52 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change From Baseline in Weight-for-age Z-Score at Week 24 | 0.17 Z-score | Standard Deviation 0.36 |
Secondary
Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26
Sweat samples were collected using an approved collection device.
Time frame: Week 24, Week 26
Population: The FAS included all enrolled subjects in Part B who were exposed to any amount of LUM/IVA in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26 | 34.4 mmol/L | Standard Deviation 14.9 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26 | 32.2 mmol/L | Standard Deviation 13.8 |
Secondary
Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale
The acceptability and palatability of LUM/IVA granules was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). The assessment was conducted in 2 steps: assessment of approved food/liquid (Evaluation 1), and assessment of approved food/liquid with LUM/IVA granules (Evaluation 2).
Time frame: Day 1
Population: The FAS included all enrolled subjects in Part B who were exposed to any amount of LUM/IVA in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 1 | Liked it Very Much | 9 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 1 | Liked it a Little | 4 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 1 | Not sure | 3 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 1 | Disliked it a Little | 0 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 1 | Disliked it Very Much | 2 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 2 | Liked it Very Much | 4 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 2 | Liked it a Little | 2 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 2 | Not sure | 4 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 2 | Disliked it a Little | 3 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 2 | Disliked it Very Much | 5 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 2 | Not sure | 6 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 1 | Liked it Very Much | 30 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 2 | Liked it Very Much | 6 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 1 | Liked it a Little | 6 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 2 | Disliked it Very Much | 15 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 1 | Not sure | 1 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 2 | Liked it a Little | 5 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 1 | Disliked it a Little | 0 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 2 | Disliked it a Little | 6 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale | Evaluation 1 | Disliked it Very Much | 1 Participants |
Secondary
Part B: Number of Cystic Fibrosis (CF)-Related Hospitalizations
Time frame: Through Week 24
Population: The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Cystic Fibrosis (CF)-Related Hospitalizations | 1 hospitalizations |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Cystic Fibrosis (CF)-Related Hospitalizations | 3 hospitalizations |
Secondary
Part B: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24
Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. Time to event data was not collected and instead, number of participants with first event were collected and are reported. Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates. However, due to less than 50% of events, time-to-first event data was not estimated. Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.
Time frame: Through Week 24
Population: The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24 | 3 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24 | 15 Participants |
Secondary
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24
Following microbial tests were performed: Burkholderia, Methicillin Resistant Staphylococcus Aureus (MRSA), Methicillin Susceptible Staphylococcus Aureus (MSSA), Pseudomonas Aeruginosa Mucoid (P. Aeruginosa Mucoid), P. Aeruginosa Non-Mucoid, P. Aeruginosa Small Colony Variant and Stenotrophomonas Maltophilia.
Time frame: Baseline and Week 24
Population: The FAS analysis set was used. Here Number Analyzed signifies those participants who were evaluated for this outcome at the specified time point..
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: P. Aeruginosa Mucoid | Negative | 19 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: MRSA | Negative | 16 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: P. Aeruginosa Mucoid | Positive | 0 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: MSSA | Negative | 12 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: P. Aeruginosa Non-Mucoid | Negative | 17 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: Burkholderia | Positive | 0 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: P. Aeruginosa Non-Mucoid | Positive | 1 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: MSSA | Positive | 6 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: P. Aeruginosa Non-Mucoid | Negative | 16 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: MRSA | Positive | 2 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: P. Aeruginosa Non-Mucoid | Positive | 3 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: MSSA | Negative | 13 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: P. Aeruginosa Small Colony Variant | Negative | 18 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: Burkholderia | Positive | 0 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: P. Aeruginosa Small Colony Variant | Positive | 0 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: MSSA | Positive | 6 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: P. Aeruginosa Small Colony Variant | Negative | 19 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24:MRSA | Negative | 17 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: P. Aeruginosa Small Colony Variant | Positive | 0 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: P. Aeruginosa Mucoid | Negative | 18 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: Stenotrophomonas Maltophilia | Negative | 17 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: Burkholderia | Negative | 19 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: Stenotrophomonas Maltophilia | Positive | 1 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: P. Aeruginosa Mucoid | Positive | 0 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: Stenotrophomonas Maltophilia | Negative | 18 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24:MRSA | Positive | 2 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: Stenotrophomonas Maltophilia | Positive | 1 Participants |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: Burkholderia | Negative | 18 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: Stenotrophomonas Maltophilia | Positive | 0 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: Burkholderia | Negative | 37 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: Burkholderia | Positive | 1 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: Burkholderia | Negative | 36 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: Burkholderia | Positive | 0 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: MRSA | Negative | 33 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: MRSA | Positive | 5 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24:MRSA | Negative | 35 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24:MRSA | Positive | 1 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: MSSA | Negative | 26 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: MSSA | Positive | 12 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: MSSA | Negative | 26 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: MSSA | Positive | 10 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: P. Aeruginosa Mucoid | Negative | 37 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: P. Aeruginosa Mucoid | Positive | 1 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: P. Aeruginosa Mucoid | Negative | 35 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: P. Aeruginosa Mucoid | Positive | 1 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: P. Aeruginosa Non-Mucoid | Negative | 35 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: P. Aeruginosa Non-Mucoid | Positive | 3 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: P. Aeruginosa Non-Mucoid | Negative | 34 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: P. Aeruginosa Non-Mucoid | Positive | 2 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: P. Aeruginosa Small Colony Variant | Negative | 38 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: P. Aeruginosa Small Colony Variant | Positive | 0 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: P. Aeruginosa Small Colony Variant | Negative | 36 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: P. Aeruginosa Small Colony Variant | Positive | 0 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: Stenotrophomonas Maltophilia | Negative | 37 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Baseline: Stenotrophomonas Maltophilia | Positive | 1 Participants |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 | Week 24: Stenotrophomonas Maltophilia | Negative | 36 Participants |
Secondary
Part B: Number of Pulmonary Exacerbations
Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria.
Time frame: Through Week 24
Population: The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Number of Pulmonary Exacerbations | 5 pulmonary exacerbations |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Number of Pulmonary Exacerbations | 20 pulmonary exacerbations |
Secondary
Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites
Time frame: Week 24
Population: The PK set for Part B included all participants who received at least 1 dose of LUM/IVA in Part B. Here Number Analyzed signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites | LUM Metabolite (M28 LUM) | 1420 ng/mL | Standard Deviation 846 |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites | IVA Metabolite (M1 IVA) | 555 ng/mL | Standard Deviation 560 |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites | IVA | 108 ng/mL | Standard Deviation 109 |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites | IVA Metabolite (M6 IVA) | 2050 ng/mL | Standard Deviation 1940 |
| Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg | Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites | LUM | 9060 ng/mL | Standard Deviation 4060 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites | IVA Metabolite (M6 IVA) | 1900 ng/mL | Standard Deviation 1430 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites | LUM | 9390 ng/mL | Standard Deviation 4830 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites | LUM Metabolite (M28 LUM) | 1510 ng/mL | Standard Deviation 752 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites | IVA | 110 ng/mL | Standard Deviation 108 |
| Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg | Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites | IVA Metabolite (M1 IVA) | 521 ng/mL | Standard Deviation 478 |