Cystic Fibrosis
Conditions
Brief summary
To evaluate the efficacy and safety of lumacaftor in combination with ivacaftor in subjects aged 6 Through 11 years with cystic fibrosis (CF), homozygous for the F508del CF transmembrane conductance regulator (CFTR) mutation
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who weigh ≥15 kg without shoes a the Screening Visit * Subjects with confirmed diagnosis of CF at the Screening Visit. * Subjects who are homozygous for the F508del CFTR mutation * Subjects with ppFEV1 of ≥70 percentage points adjusted for age, sex, and height * Subjects with a screening LCI2.5 result greater than or equal to 7.5
Exclusion criteria
* History of any comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. * Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject * Clinically significant abnormalities in hemoglobin, liver function, or renal function at the Screening Visit. * An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1 * History of solid organ or hematological transplantation at the Screening Visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) Through Week 24 | Baseline, Through Week 24 | Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | Baseline, Week 24 | BMI was defined as weight in kg divided by height in square meter (m\^2). |
| Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24 | Baseline, Through Week 24 | The CFQ-R is a validated participant-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. |
| Absolute Change From Baseline in Lung Clearance Index 5.0 (LCI5.0) Through Week 24 | Baseline, Through Week 24 | LCI is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value. |
| Absolute Change From Baseline in Sweat Chloride at Week 24 | Baseline, Week 24 | Sweat samples were collected using an approved collection device. |
| Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24 | Baseline, Through Week 24 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Wang standards were used to calculate ppFEV1 (for age, gender, race, and height). |
| Relative Change From Baseline in ppFEV1 Through Week 24 | Baseline, Through Week 24 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Wang standards were used to calculate ppFEV1 (for age, gender, race, and height). |
| 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 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. 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. |
| Absolute Change From Baseline in Weight at Week 24 | Baseline, Week 24 | — |
| Average Absolute Change From Baseline in Sweat Chloride at Day 15 and 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. Change from Baseline in sweat chloride at Day 15 and Week 4 was calculated. The average of the 2 values (Change at Day 15 and Week 4) was reported. |
| Absolute Change From Baseline in Height at Week 24 | Baseline, Week 24 | — |
| 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. 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. |
| Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 | Baseline, Through 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. |
| Number of Pulmonary Exacerbation Events | Baseline through Week 24 | Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. The number of events were reported. |
| Percentage of Participants With At Least 1 Pulmonary Exacerbation Event | Baseline through Week 24 | Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. |
| Time-to-first Pulmonary Exacerbation | Baseline through Week 24 | Time-to-first pulmonary exacerbation was analyzed using the Kaplan-Meier estimates. Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to Week 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. Any AE that increased in severity or newly developed at or after initial dosing of study drug to Week 28 was considered treatment-emergent. |
| Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor | For Ctrough,ave: before morning dose on Week 4 and 24; For C3-6h,ave: 3 to 6 hours after morning dose on Day 1, 15 and Week 4 | Ctrough,ave is average of individual pre-dose observed concentrations across Week 4 and 24. C3-6h,ave is average of individual 3 to 6 hours post-dose observed concentrations across Day 1, 15 and Week 4. This outcome was not planned to be assessed in Placebo arm. |
| 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. 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. |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 206 participants were randomized in the study, of which 204 participants were exposed to study treatment (101 participants received 'Placebo' and 103 participants received '(lumacaftor \[LUM\] / ivacaftor \[IVA\])'.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks. | 101 |
| LUM/IVA Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks. | 103 |
| Total | 204 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | LUM/IVA | Total |
|---|---|---|---|
| Age, Continuous | 8.9 years STANDARD_DEVIATION 1.59 | 8.7 years STANDARD_DEVIATION 1.6 | 8.8 years STANDARD_DEVIATION 1.59 |
| Sex: Female, Male Female | 58 Participants | 63 Participants | 121 Participants |
| Sex: Female, Male Male | 43 Participants | 40 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 0 / 103 |
| other Total, other adverse events | 98 / 101 | 98 / 103 |
| serious Total, serious adverse events | 11 / 101 | 13 / 103 |
Outcome results
Primary
Absolute Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) Through Week 24
Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI2.5 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, Through Week 24
Population: Full Analysis Set (FAS) included all randomized participants who received any amount of study drug. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) Through Week 24 | 0.08 Ratio | Standard Error 0.13 |
| LUM/IVA | Absolute Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) Through Week 24 | -1.01 Ratio | Standard Error 0.13 |
Comparison: Analysis was performed using mixed-effects model for repeated measures (MMRM). The model included treatment, visit and treatment-by-visit interaction as fixed effects; and participant as a random effect with adjustments for baseline, weight (less than \[\<\] 25 kilogram \[kg\] versus greater than or equal to \[\>=\] 25 kg) and percent predicted forced expiratory volume in 1 second (FEV1) severity (\<90 versus \>=90) at screening.p-value: <0.000195% CI: [-1.43, -0.75]MMRM
Secondary
Absolute Change From Baseline in 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 evaluate how a single data point compares to a standard. It describes 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). The BMI-for-age z-scores were calculated using National Center for Health Statistics growth charts.
Time frame: Baseline, Week 24
Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in BMI-for-age Z-score at Week 24 | 0.05 Z-score | Standard Error 0.04 |
| LUM/IVA | Absolute Change From Baseline in BMI-for-age Z-score at Week 24 | 0.08 Z-score | Standard Error 0.04 |
Secondary
Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
BMI was defined as weight in kg divided by height in square meter (m\^2).
Time frame: Baseline, Week 24
Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | 0.27 Kg/m^2 | Standard Error 0.07 |
| LUM/IVA | Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | 0.38 Kg/m^2 | Standard Error 0.07 |
Secondary
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
The CFQ-R is a validated participant-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, Through Week 24
Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24 | 3.0 Units on a scale | Standard Error 1 |
| LUM/IVA | Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24 | 5.5 Units on a scale | Standard Error 1 |
Secondary
Absolute Change From Baseline in Height at Week 24
Time frame: Baseline, Week 24
Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Height at Week 24 | 2.6 Centimeter (cm) | Standard Error 0.1 |
| LUM/IVA | Absolute Change From Baseline in Height at Week 24 | 2.9 Centimeter (cm) | Standard Error 0.1 |
Secondary
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. 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: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Height-for-age Z-score at Week 24 | 0.00 Z-score | Standard Error 0.02 |
| LUM/IVA | Absolute Change From Baseline in Height-for-age Z-score at Week 24 | 0.03 Z-score | Standard Error 0.02 |
Secondary
Absolute Change From Baseline in Lung Clearance Index 5.0 (LCI5.0) Through Week 24
LCI is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI5.0 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, Through Week 24
Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Lung Clearance Index 5.0 (LCI5.0) Through Week 24 | 0.08 Ratio | Standard Error 0.05 |
| LUM/IVA | Absolute Change From Baseline in Lung Clearance Index 5.0 (LCI5.0) Through Week 24 | -0.36 Ratio | Standard Error 0.05 |
Secondary
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Wang standards were used to calculate ppFEV1 (for age, gender, race, and height).
Time frame: Baseline, Through Week 24
Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24 | -1.3 Percent predicted of FEV1 | Standard Error 0.8 |
| LUM/IVA | Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24 | 1.1 Percent predicted of FEV1 | Standard Error 0.8 |
Secondary
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: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Sweat Chloride at Week 24 | 3.2 mmol/L | Standard Error 1.3 |
| LUM/IVA | Absolute Change From Baseline in Sweat Chloride at Week 24 | -21.6 mmol/L | Standard Error 1.3 |
Secondary
Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through 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, Through Week 24
Population: FAS. Here, 'Number of participants analyzed' = those participants who were evaluable for this endpoint and 'Number Analyzed' = those participants who were evaluable at the specified time points for each arm, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 | Change Through Week 24: Effectiveness | 0.6 Units on a scale | Standard Error 1.5 |
| Placebo | Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 | Change Through Week 24: Convenience | 9.9 Units on a scale | Standard Error 1.2 |
| Placebo | Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 | Change Through Week 24: Global Score | -2.3 Units on a scale | Standard Error 1.6 |
| Placebo | Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 | Change Through Week 24: Side Effects | 0.4 Units on a scale | Standard Error 0.8 |
| LUM/IVA | Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 | Change Through Week 24: Global Score | -1.4 Units on a scale | Standard Error 1.6 |
| LUM/IVA | Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 | Change Through Week 24: Effectiveness | 1.7 Units on a scale | Standard Error 1.5 |
| LUM/IVA | Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 | Change Through Week 24: Side Effects | -1.0 Units on a scale | Standard Error 0.8 |
| LUM/IVA | Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 | Change Through Week 24: Convenience | 11.9 Units on a scale | Standard Error 1.2 |
Secondary
Absolute Change From Baseline in Weight at Week 24
Time frame: Baseline, Week 24
Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Weight at Week 24 | 1.7 Kg | Standard Error 0.2 |
| LUM/IVA | Absolute Change From Baseline in Weight at Week 24 | 2.0 Kg | Standard Error 0.1 |
Secondary
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. 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: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Weight-for-age Z-score at Week 24 | 0.02 Z-score | Standard Error 0.02 |
| LUM/IVA | Absolute Change From Baseline in Weight-for-age Z-score at Week 24 | 0.06 Z-score | Standard Error 0.02 |
Secondary
Average Absolute Change From Baseline in Sweat Chloride at 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. Change from Baseline in sweat chloride at Day 15 and Week 4 was calculated. The average of the 2 values (Change at Day 15 and Week 4) was reported.
Time frame: Baseline, Day 15 and Week 4
Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Average Absolute Change From Baseline in Sweat Chloride at Day 15 and Week 4 | 0.8 Millimole per liter (mmol/L) | Standard Error 1 |
| LUM/IVA | Average Absolute Change From Baseline in Sweat Chloride at Day 15 and Week 4 | -20.0 Millimole per liter (mmol/L) | Standard Error 1 |
Secondary
Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor
Ctrough,ave is average of individual pre-dose observed concentrations across Week 4 and 24. C3-6h,ave is average of individual 3 to 6 hours post-dose observed concentrations across Day 1, 15 and Week 4. This outcome was not planned to be assessed in Placebo arm.
Time frame: For Ctrough,ave: before morning dose on Week 4 and 24; For C3-6h,ave: 3 to 6 hours after morning dose on Day 1, 15 and Week 4
Population: Pharmacokinetic (PK) set included all randomized participants who received any amount of study drug and had a PK assessment. Here, 'Number of participants analyzed' = those participants who were evaluable for this endpoint and 'Number Analyzed' = those participants who were evaluable at the specified time points for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor | LUM: Ctrough,ave | 10200 Nanogram per milliliter (ng/mL) | Standard Deviation 4460 |
| Placebo | Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor | LUM: C3-6h,ave | 20600 Nanogram per milliliter (ng/mL) | Standard Deviation 6560 |
| Placebo | Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor | IVA: Ctrough,ave | 107 Nanogram per milliliter (ng/mL) | Standard Deviation 91.2 |
| Placebo | Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor | IVA: C3-6h,ave | 821 Nanogram per milliliter (ng/mL) | Standard Deviation 348 |
Secondary
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. Any AE that increased in severity or newly developed at or after initial dosing of study drug to Week 28 was considered treatment-emergent.
Time frame: Baseline up to Week 28
Population: Safety Set included all participants who were exposed to any amount of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With Any Treatment-Emergent AEs | 98 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With Treatment-Emergent SAEs | 11 participants |
| LUM/IVA | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With Any Treatment-Emergent AEs | 98 participants |
| LUM/IVA | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With Treatment-Emergent SAEs | 13 participants |
Secondary
Number of Pulmonary Exacerbation Events
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. The number of events were reported.
Time frame: Baseline through Week 24
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Pulmonary Exacerbation Events | 18 Pulmonary exacerbation events |
| LUM/IVA | Number of Pulmonary Exacerbation Events | 24 Pulmonary exacerbation events |
Secondary
Percentage of Participants With At Least 1 Pulmonary Exacerbation Event
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time frame: Baseline through Week 24
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With At Least 1 Pulmonary Exacerbation Event | 14.9 Percentage of participants |
| LUM/IVA | Percentage of Participants With At Least 1 Pulmonary Exacerbation Event | 19.4 Percentage of participants |
Secondary
Relative Change From Baseline in ppFEV1 Through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Wang standards were used to calculate ppFEV1 (for age, gender, race, and height).
Time frame: Baseline, Through Week 24
Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Relative Change From Baseline in ppFEV1 Through Week 24 | -0.9 Percent change | Standard Error 1 |
| LUM/IVA | Relative Change From Baseline in ppFEV1 Through Week 24 | 2.2 Percent change | Standard Error 1 |
Secondary
Time-to-first Pulmonary Exacerbation
Time-to-first pulmonary exacerbation was analyzed using the Kaplan-Meier estimates. Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time frame: Baseline through Week 24
Population: FAS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time-to-first Pulmonary Exacerbation | NA Days |
| LUM/IVA | Time-to-first Pulmonary Exacerbation | NA Days |