Cystic Fibrosis
Conditions
Brief summary
The study evaluates the long-term safety and tolerability of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del mutation
Interventions
DRUGELX/TEZ/IVA
Fixed-dose combination (FDC) tablet for oral administration.
DRUGIVA
Tablet for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completed study drug treatment in a parent study i.e.VX17-445-102 (NCT03525444) and VX17-445-103 (NCT03525548); or had study drug interruption(s) in a parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study.
Exclusion criteria
* History of drug intolerance in a parent study that would pose an additional risk to the subject in the opinion of the investigator. * Current participation in an investigational drug trial (other than a parent study) Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment Period: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From Day 1 up to Week 196 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/105 Efficacy Set | From Baseline at Week 192 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA. |
| Absolute Change in Sweat Chloride (SwCl) for 102/105 Efficacy Set | From Baseline at Week 192 | Sweat samples were collected using an approved collection device. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA. |
| Absolute Change in Sweat Chloride (SwCl) for 103/105 Efficacy Set | From Baseline at Week 192 | Sweat samples were collected using an approved collection device. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA. |
| Number of Pulmonary Exacerbations (PEx) for 102/105 Efficacy Set | From Baseline at Week 192 | 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 Pulmonary Exacerbations (PEx) for 103/105 Efficacy Set | From Baseline at Week 192 | 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 PEx for 102/105 Efficacy Set | From Baseline at Week 192 | Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx 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 PEx for 103/105 Efficacy Set | From Baseline at Week 192 | Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx 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. |
| Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 102/105 Efficacy Set | From Baseline at Week 192 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA. |
| Absolute Change in Body Mass Index (BMI) for 103/105 Efficacy Set | From Baseline at Week 192 | BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA. |
| Absolute Change in BMI Z-score for 102/105 Efficacy Set | From Baseline at Week 192 | 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. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA. |
| Absolute Change in BMI Z-score for 103/105 Efficacy Set | From Baseline at Week 192 | 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. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA. |
| Absolute Change in Body Weight for 102/105 Efficacy Set | From Baseline at Week 192 | This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA. |
| Absolute Change in Body Weight for 103/105 Efficacy Set | From Baseline at Week 192 | This analysis set included study 103 parent study participants who received TEZ/IVA and ELX/TEZ/IVA. |
| Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 102/105 Efficacy Set | From Baseline at Week 192 | 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, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA. |
| Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/105 Efficacy Set | From Baseline at Week 192 | 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, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. This analysis set included study 103 parent study participants who received TEZ/IVA and ELX/TEZ/IVA. |
| Absolute Change in Body Mass Index (BMI) for 102/105 Efficacy Set | From Baseline at Week 192 | BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA. |
Countries
Australia, Austria, Belgium, Canada, Czechia, France, Germany, Greece, Italy, Netherlands, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted as a single period i.e. treatment period in countries including United States (US) with commercially-available ELX/TEZ/IVA. The regional protocol for other countries without commercially-available ELX/TEZ/IVA was amended so that participants in these countries had the opportunity to participate for up to an additional 48 weeks in extension period.
Pre-assignment details
A total 507 participants were enrolled in this study from the parent studies VX17-445-102 (NCT03525444) and VX17-445-103 (NCT03525548). One participant was enrolled but did not receive any dose in this study.
Participants by arm
| Arm | Count |
|---|---|
| ELX/TEZ/IVA Treatment Period: Participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 192 weeks.
Extension Period: Participants from certain countries participated in extension period and continued to received ELX 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h in the extension period for 48 weeks. | 506 |
| Total | 506 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 0 |
| Overall Study | Commercial drug is Available for participant | 48 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Enrolled but never dosed | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 0 |
| Overall Study | Not enrolled in 105 study | 0 | 3 |
| Overall Study | Other | 58 | 0 |
| Overall Study | Other non-compliance | 2 | 0 |
| Overall Study | Physician Decision | 6 | 0 |
| Overall Study | Withdrawal of consent (not due to AE) | 18 | 0 |
Baseline characteristics
| Characteristic | ELX/TEZ/IVA |
|---|---|
| Age, Continuous | 26.7 years STANDARD_DEVIATION 10.7 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 21 Participants |
| Race/Ethnicity, Customized Multiple | 3 Participants |
| Race/Ethnicity, Customized Not collected per local regulations | 25 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 460 Participants |
| Race/Ethnicity, Customized Other | 3 Participants |
| Race/Ethnicity, Customized White | 470 Participants |
| Sex: Female, Male Female | 251 Participants |
| Sex: Female, Male Male | 255 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 506 | 0 / 11 |
| other Total, other adverse events | 501 / 506 | 7 / 11 |
| serious Total, serious adverse events | 175 / 506 | 0 / 11 |
Outcome results
Primary
Treatment Period: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From Day 1 up to Week 196
Population: The Open-Label Safety Set (OL-SS) included all participants who had received at least 1 dose of study drug in this open label study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ELX/TEZ/IVA | Treatment Period: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 175 Participants |
| ELX/TEZ/IVA | Treatment Period: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 504 Participants |
Secondary
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 102/105 Efficacy Set
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, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Time frame: From Baseline at Week 192
Population: OL-FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome. Here Number Analyzed signifies participants who were evaluable for the specified category. Baseline was defined as the parent study baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 102/105 Efficacy Set | Placebo-ELX/TEZ/IVA | 15.3 units on a scale | Standard Error 1.5 |
| ELX/TEZ/IVA | Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 102/105 Efficacy Set | ELX/TEZ/IVA-ELX/TEZ/IVA | 18.3 units on a scale | Standard Error 1.5 |
Secondary
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/105 Efficacy Set
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, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. This analysis set included study 103 parent study participants who received TEZ/IVA and ELX/TEZ/IVA.
Time frame: From Baseline at Week 192
Population: OL-FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome. Here Number Analyzed signifies participants who were evaluable for the specified category. Baseline was defined as the parent study baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/105 Efficacy Set | TEZ/IVA-ELX/TEZ/IVA | 14.8 units on a scale | Standard Error 2.6 |
| ELX/TEZ/IVA | Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/105 Efficacy Set | ELX/TEZ/IVA-ELX/TEZ/IVA | 17.6 units on a scale | Standard Error 2.4 |
Secondary
Absolute Change in BMI Z-score for 102/105 Efficacy Set
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. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Time frame: From Baseline at Week 192
Population: OL-FAS. Here Overall Number of Participants Analyzed signifies those participants who were \<=20 years of age at Baseline. Here Number Analyzed signifies participants who were evaluable for the specified category. Baseline was defined as the parent study baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change in BMI Z-score for 102/105 Efficacy Set | Placebo-ELX/TEZ/IVA | 0.24 z-score | Standard Error 0.09 |
| ELX/TEZ/IVA | Absolute Change in BMI Z-score for 102/105 Efficacy Set | ELX/TEZ/IVA-ELX/TEZ/IVA | 0.18 z-score | Standard Error 0.09 |
Secondary
Absolute Change in BMI Z-score for 103/105 Efficacy Set
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. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Time frame: From Baseline at Week 192
Population: OL-FAS. Here Overall Number of Participants Analyzed signifies those participants who were \<=20 years of age at Baseline. Here Number Analyzed signifies participants who were evaluable for the specified category. Baseline was defined as the parent study baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change in BMI Z-score for 103/105 Efficacy Set | TEZ/IVA-ELX/TEZ/IVA | 0.36 z-score | Standard Error 0.14 |
| ELX/TEZ/IVA | Absolute Change in BMI Z-score for 103/105 Efficacy Set | ELX/TEZ/IVA-ELX/TEZ/IVA | 0.24 z-score | Standard Error 0.15 |
Secondary
Absolute Change in Body Mass Index (BMI) for 102/105 Efficacy Set
BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Time frame: From Baseline at Week 192
Population: OL-FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome. Here Number Analyzed signifies participants who were evaluable for the specified category. Baseline was defined as the parent study baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change in Body Mass Index (BMI) for 102/105 Efficacy Set | Placebo-ELX/TEZ/IVA | 1.81 kilogram per meter square (kg/m^2) | Standard Error 0.16 |
| ELX/TEZ/IVA | Absolute Change in Body Mass Index (BMI) for 102/105 Efficacy Set | ELX/TEZ/IVA-ELX/TEZ/IVA | 1.74 kilogram per meter square (kg/m^2) | Standard Error 0.16 |
Secondary
Absolute Change in Body Mass Index (BMI) for 103/105 Efficacy Set
BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Time frame: From Baseline at Week 192
Population: OL-FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome. Here Number Analyzed signifies participants who were evaluable for the specified category. Baseline was defined as the parent study baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change in Body Mass Index (BMI) for 103/105 Efficacy Set | TEZ/IVA-ELX/TEZ/IVA | 1.72 kg/m^2 | Standard Error 0.24 |
| ELX/TEZ/IVA | Absolute Change in Body Mass Index (BMI) for 103/105 Efficacy Set | ELX/TEZ/IVA-ELX/TEZ/IVA | 1.85 kg/m^2 | Standard Error 0.22 |
Secondary
Absolute Change in Body Weight for 102/105 Efficacy Set
This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Time frame: From Baseline at Week 192
Population: OL-FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome. Here Number Analyzed signifies participants who were evaluable for the specified category. Baseline was defined as the parent study baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change in Body Weight for 102/105 Efficacy Set | ELX/TEZ/IVA-ELX/TEZ/IVA | 6.0 kg | Standard Error 0.5 |
| ELX/TEZ/IVA | Absolute Change in Body Weight for 102/105 Efficacy Set | Placebo-ELX/TEZ/IVA | 6.6 kg | Standard Error 0.5 |
Secondary
Absolute Change in Body Weight for 103/105 Efficacy Set
This analysis set included study 103 parent study participants who received TEZ/IVA and ELX/TEZ/IVA.
Time frame: From Baseline at Week 192
Population: OL-FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome. Here Number Analyzed signifies participants who were evaluable for the specified category. Baseline was defined as the parent study baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change in Body Weight for 103/105 Efficacy Set | TEZ/IVA-ELX/TEZ/IVA | 6.1 kg | Standard Error 0.8 |
| ELX/TEZ/IVA | Absolute Change in Body Weight for 103/105 Efficacy Set | ELX/TEZ/IVA-ELX/TEZ/IVA | 6.3 kg | Standard Error 0.7 |
Secondary
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 102/105 Efficacy Set
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Time frame: From Baseline at Week 192
Population: OL-FAS is defined as all enrolled participants who received at least 1 dose of study drug in this open label study. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome. Here Number Analyzed signifies participants who were evaluable for the specified category. Baseline was defined as the parent study baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 102/105 Efficacy Set | Placebo-ELX/TEZ/IVA | 15.3 percentage points | Standard Error 0.8 |
| ELX/TEZ/IVA | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 102/105 Efficacy Set | ELX/TEZ/IVA-ELX/TEZ/IVA | 13.8 percentage points | Standard Error 0.8 |
Secondary
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/105 Efficacy Set
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Time frame: From Baseline at Week 192
Population: OL-FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome. Here Number Analyzed signifies participants who were evaluable for the specified category. Baseline was defined as the parent study baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/105 Efficacy Set | TEZ/IVA-ELX/TEZ/IVA | 10.9 percentage points | Standard Error 1.3 |
| ELX/TEZ/IVA | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/105 Efficacy Set | ELX/TEZ/IVA-ELX/TEZ/IVA | 10.7 percentage points | Standard Error 1.3 |
Secondary
Absolute Change in Sweat Chloride (SwCl) for 102/105 Efficacy Set
Sweat samples were collected using an approved collection device. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Time frame: From Baseline at Week 192
Population: OL-FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome. Here Number Analyzed signifies participants who were evaluable for the specified category. Baseline was defined as the parent study baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change in Sweat Chloride (SwCl) for 102/105 Efficacy Set | Placebo-ELX/TEZ/IVA | -47.0 millimole per liter (mmol/L) | Standard Error 1.6 |
| ELX/TEZ/IVA | Absolute Change in Sweat Chloride (SwCl) for 102/105 Efficacy Set | ELX/TEZ/IVA-ELX/TEZ/IVA | -45.3 millimole per liter (mmol/L) | Standard Error 1.6 |
Secondary
Absolute Change in Sweat Chloride (SwCl) for 103/105 Efficacy Set
Sweat samples were collected using an approved collection device. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Time frame: From Baseline at Week 192
Population: OL-FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome. Here Number Analyzed signifies participants who were evaluable for the specified category. Baseline was defined as the parent study baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change in Sweat Chloride (SwCl) for 103/105 Efficacy Set | TEZ/IVA-ELX/TEZ/IVA | -48.2 mmol/L | Standard Error 3.8 |
| ELX/TEZ/IVA | Absolute Change in Sweat Chloride (SwCl) for 103/105 Efficacy Set | ELX/TEZ/IVA-ELX/TEZ/IVA | -48.2 mmol/L | Standard Error 3.5 |
Secondary
Number of Pulmonary Exacerbations (PEx) for 102/105 Efficacy Set
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: From Baseline at Week 192
Population: Cumulative TC Efficacy Set 102/105 included all participants who were randomized to TC ELX/TEZ/IVA and received at least 1 dose of study drug during the parent study 102 and/or received at least 1 dose of study drug during this open label study. Baseline was defined as the parent study baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ELX/TEZ/IVA | Number of Pulmonary Exacerbations (PEx) for 102/105 Efficacy Set | 174 PEx events |
Secondary
Number of Pulmonary Exacerbations (PEx) for 103/105 Efficacy Set
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: From Baseline at Week 192
Population: Cumulative TC Efficacy Set 103/105 included all participants who were randomized to TC ELX/TEZ/IVA and received at least 1 dose of study drug during the parent study 103 and/or received at least 1 dose of study drug during this open label study. Baseline was defined as the parent study baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ELX/TEZ/IVA | Number of Pulmonary Exacerbations (PEx) for 103/105 Efficacy Set | 43 PEx events |
Secondary
Time to First PEx for 102/105 Efficacy Set
Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx 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: From Baseline at Week 192
Population: Cumulative TC Efficacy Set 102/105 included all participants who were randomized to TC ELX/TEZ/IVA and received at least 1 dose of study drug during the parent study 102 and/or received at least 1 dose of study drug during this open label study. Baseline was defined as the parent study baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ELX/TEZ/IVA | Time to First PEx for 102/105 Efficacy Set | NA days |
Secondary
Time to First PEx for 103/105 Efficacy Set
Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx 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: From Baseline at Week 192
Population: Cumulative TC Efficacy Set 103/105 included all participants who were randomized to TC ELX/TEZ/IVA and received at least 1 dose of study drug during the parent study 103 and/or received at least 1 dose of study drug during this open label study. Baseline was defined as the parent study baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ELX/TEZ/IVA | Time to First PEx for 103/105 Efficacy Set | NA days |