Cystic Fibrosis
Conditions
Brief summary
This is a Phase 4, randomized, double-blind, placebo-controlled, parallel-group study in subjects aged 12 years and older with CF who are homozygous for the F508del-CFTR mutation. This study is designed to evaluate the effect of LUM/IVA on exercise tolerance in subjects with CF, homozygous for the F508del-CFTR mutation.
Interventions
DRUGLUM/IVA
DRUGPlacebo
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Homozygous for the F508del-CFTR mutation * Confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis * Stable CF disease as judged by the investigator * Forced expiratory volume in 1 second (FEV1) at least 40% and not greater than 90% of predicted
Exclusion criteria
* History of any comorbidity that might confound the results of the study, interfere with the use of cardiopulmonary exercise tests (CPETs) as an assessment, or pose an additional risk in administering study drug to the subject * Any previous exposure to LUM or IVA * History of cardiac arrhythmia, ischemic heart disease, congestive heart failure, or other clinically significant cardiac condition, or medical condition requiring chronic use of a beta blocker, non-dihydropyridine calcium channel blocker, or other cardiac medication known to affect exercise tolerance * History of solid organ or hematological transplantation * For subjects under 18 years of age at Screening, except those who have had bilateral lens removal, selected findings on a screening ophthalmologic examination will be exclusionary * Using or expected to require any concomitant medication that is prohibited in this study * History of alcohol or drug abuse, as deemed by the investigator, in the past year, including but not limited to cannabis, cocaine, and opiates * Participation in an investigational drug study within 30 days before the Screening Visit * Pregnant or nursing females; males with a female partner who is pregnant or nursing * Colonization with organisms associated with a more rapid decline in pulmonary status
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24 | Baseline, Week 24 | CPET was used to assess change in exercise tolerance, as measured by VO2max. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Oxygen Consumption (VO2) at Anaerobic Threshold at Week 24 | Baseline, Week 24 | Anaerobic threshold was defined as the exercise intensity at which lactate starts to accumulate. |
| Relative (Percent) Change From Baseline in Exercise Duration During CPET at Week 24 | Baseline, Week 24 | Exercise duration is defined as the time at the termination of CPET exercise minus the corresponding time when CPET starts for each CPET exercise. |
| Absolute Change From Baseline in Exercise Duration During CPET at Week 24 | Baseline, Week 24 | Exercise duration is defined as the time at the termination of CPET exercise minus the corresponding time when CPET starts for each CPET exercise. |
| Relative (Percent) Change From Baseline in VO2 at Anaerobic Threshold at Week 24 | Baseline, Week 24 | Anaerobic threshold was defined as the exercise intensity at which lactate starts to accumulate. |
| Absolute Change From Baseline in Functional VO2 Gain at Week 24 | Baseline, Week 24 | — |
| Relative (Percent) Change From Baseline in Functional VO2 Gain at Week 24 | Baseline, Week 24 | — |
| Absolute Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24 | Baseline, Week 24 | — |
| Relative (Percent) Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24 | Baseline, Week 24 | — |
| 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. |
| Relative (Percent) 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. |
| 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). |
| Absolute Change From Baseline in VO2max During CPET at Week 24 | Baseline, Week 24 | CPET was used to assess change in exercise tolerance, as measured by VO2max. |
| Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24 | Baseline, Week 24 | The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life. |
| Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Baseline, Week 24 | The PHQ-8 is an eight item self-reported measure of depression. Each item is rated on a scale ranging from 0 (not at all) to 3 (nearly every day). Total score is the sum of individual eight items and ranges from 0 to 24, with higher scores indicating more severe depression symptoms. Total score of 0 to 5 indicates none to minimal depression, 6 to 10 indicates mild depression, 11 to 15 indicates moderate depression, 16 to 20 indicates moderately severe depression and 21 to 24 indicates severe depression. |
| Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Baseline, Week 24 | The GAD-7 is a seven item, self-reported measurement of GAD severity. Each item is rated on a scale ranging from 0 (not at all) to 3 (nearly every day). Total score is the sum of individual seven items and ranges from 0 to 21, with higher scores indicating more severe anxiety symptoms. Total score of 0 to 5 indicates none to minimal anxiety, 6 to 10 indicates mild anxiety, 11 to 15 indicates moderate anxiety, 16 to 21 indicates severe anxiety. |
| Absolute Change From Baseline in Daily Physical Activity Counts as Determined by Actigraphy at Week 24 | Baseline, Week 24 | Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily physical activity counts. |
| Relative (Percent) Change From Baseline in Physical Activity as Determined by Actigraphy at Week 24 | Baseline, Week 24 | Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily physical activities. |
| Absolute Change From Baseline in Duration of Sleep Time at Week 24 | Baseline, Week 24 | Participants were provided with a wrist-worn actigraphy device which continuously collected data about sleep duration and quality. |
| Relative (Percent) Change From Baseline in Duration of Sleep Time at Week 24 | Baseline, Week 24 | Participants were provided with a wrist-worn actigraphy device which continuously collected data about sleep duration and quality. |
| Absolute Change From Baseline in Time Above Sedentary Duration at Week 24 | Baseline, Week 24 | Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily activities and sleep duration and quality. |
| Relative (Percent) Change From Baseline in Time Above Sedentary Duration at Week 24 | Baseline, Week 24 | Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily activities and sleep duration and quality. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Week 28 | — |
| Relative (Percent) Change From Baseline in BMI at Week 24 | Baseline, Week 24 | BMI was defined as weight in kg divided by height in m\^2. |
Countries
Australia, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to LUM/IVA fixed-dose combination tablet orally q12h for 24 weeks. | 36 |
| LUM/IVA Participants received LUM 400 mg/IVA 250 mg fixed-dose combination tablet orally q12h for 24 weeks. | 34 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Noncompliance | 0 | 1 |
Baseline characteristics
| Characteristic | LUM/IVA | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 24.9 years STANDARD_DEVIATION 10.17 | 25.5 years STANDARD_DEVIATION 10.33 | 26.1 years STANDARD_DEVIATION 10.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 70 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 34 Participants | 70 Participants | 36 Participants |
| Sex: Female, Male Female | 13 Participants | 31 Participants | 18 Participants |
| Sex: Female, Male Male | 21 Participants | 39 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 34 |
| other Total, other adverse events | 34 / 36 | 28 / 34 |
| serious Total, serious adverse events | 9 / 36 | 15 / 34 |
Outcome results
Primary
Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24
CPET was used to assess change in exercise tolerance, as measured by VO2max.
Time frame: Baseline, Week 24
Population: The Full Analysis Set (FAS) included all randomized participants who received any amount of study drug. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24 | -3.5 percent change |
| LUM/IVA | Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24 | -6.6 percent change |
p-value: 0.302195% CI: [-9.2, 2.9]Mixed effects model for repeated measure
Secondary
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: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | 0.3 kg/m^2 |
| LUM/IVA | Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | 0.5 kg/m^2 |
p-value: 0.396195% CI: [-0.3, 0.6]Mixed effects model for repeated measure
Secondary
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24
The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24 | -6.1 units on a scale |
| LUM/IVA | Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24 | 0.1 units on a scale |
p-value: 0.125795% CI: [-1.8, 14.1]Mixed effects model for repeated measure
Secondary
Absolute Change From Baseline in Daily Physical Activity Counts as Determined by Actigraphy at Week 24
Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily physical activity counts.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Daily Physical Activity Counts as Determined by Actigraphy at Week 24 | -23239 physical activity counts per day | Standard Deviation 73936.4 |
| LUM/IVA | Absolute Change From Baseline in Daily Physical Activity Counts as Determined by Actigraphy at Week 24 | -22409 physical activity counts per day | Standard Deviation 52450.1 |
Secondary
Absolute Change From Baseline in Duration of Sleep Time at Week 24
Participants were provided with a wrist-worn actigraphy device which continuously collected data about sleep duration and quality.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Duration of Sleep Time at Week 24 | -0.4 hours | Standard Deviation 0.88 |
| LUM/IVA | Absolute Change From Baseline in Duration of Sleep Time at Week 24 | 0.1 hours | Standard Deviation 0.74 |
Secondary
Absolute Change From Baseline in Exercise Duration During CPET at Week 24
Exercise duration is defined as the time at the termination of CPET exercise minus the corresponding time when CPET starts for each CPET exercise.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Exercise Duration During CPET at Week 24 | -2.1 seconds |
| LUM/IVA | Absolute Change From Baseline in Exercise Duration During CPET at Week 24 | -17.4 seconds |
p-value: 0.232895% CI: [-40.8, 10.1]Mixed effects model for repeated measure
Secondary
Absolute Change From Baseline in Functional VO2 Gain at Week 24
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Functional VO2 Gain at Week 24 | 0.07 milliliter per minute per watt |
| LUM/IVA | Absolute Change From Baseline in Functional VO2 Gain at Week 24 | -0.53 milliliter per minute per watt |
p-value: 0.022695% CI: [-1.12, -0.09]Mixed effects model for repeated measure
Secondary
Absolute Change From Baseline in Oxygen Consumption (VO2) at Anaerobic Threshold at Week 24
Anaerobic threshold was defined as the exercise intensity at which lactate starts to accumulate.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Oxygen Consumption (VO2) at Anaerobic Threshold at Week 24 | 94.6 milliliter per minute |
| LUM/IVA | Absolute Change From Baseline in Oxygen Consumption (VO2) at Anaerobic Threshold at Week 24 | -55.1 milliliter per minute |
p-value: 0.043995% CI: [-295, -4.2]Mixed effects model for repeated measure
Secondary
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: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 | -4.0 percentage of predicted FEV1 |
| LUM/IVA | Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 | -0.6 percentage of predicted FEV1 |
p-value: 0.14695% CI: [-1.2, 8.1]Mixed effects model for repeated measure
Secondary
Absolute Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24 | 0.5 ratio |
| LUM/IVA | Absolute Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24 | 0.8 ratio |
p-value: 0.640995% CI: [-0.9, 1.5]Mixed effects model for repeated measure
Secondary
Absolute Change From Baseline in Time Above Sedentary Duration at Week 24
Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily activities and sleep duration and quality.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Time Above Sedentary Duration at Week 24 | -0.7 hours | Standard Deviation 1.48 |
| LUM/IVA | Absolute Change From Baseline in Time Above Sedentary Duration at Week 24 | -0.7 hours | Standard Deviation 2.09 |
Secondary
Absolute Change From Baseline in VO2max During CPET at Week 24
CPET was used to assess change in exercise tolerance, as measured by VO2max.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in VO2max During CPET at Week 24 | -1.3 milliliter per kilogram per minute |
| LUM/IVA | Absolute Change From Baseline in VO2max During CPET at Week 24 | -2.7 milliliter per kilogram per minute |
p-value: 0.120395% CI: [-3.1, 0.4]Mixed effects model for repeated measure
Secondary
Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores
The GAD-7 is a seven item, self-reported measurement of GAD severity. Each item is rated on a scale ranging from 0 (not at all) to 3 (nearly every day). Total score is the sum of individual seven items and ranges from 0 to 21, with higher scores indicating more severe anxiety symptoms. Total score of 0 to 5 indicates none to minimal anxiety, 6 to 10 indicates mild anxiety, 11 to 15 indicates moderate anxiety, 16 to 21 indicates severe anxiety.
Time frame: Baseline, Week 24
Population: FAS. Here Number Analyzed signifies those participants who were evaluated for this outcome at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Baseline: Severe | 0 participants |
| Placebo | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Baseline: None to minimal | 31 participants |
| Placebo | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Week 24: None to minimal | 26 participants |
| Placebo | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Baseline: Mild | 5 participants |
| Placebo | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Week 24: Mild | 6 participants |
| Placebo | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Baseline: Moderate | 0 participants |
| Placebo | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Week 24: Severe | 0 participants |
| Placebo | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Week 24: Moderate | 1 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Week 24: Severe | 0 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Week 24: Mild | 3 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Baseline: Mild | 5 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Baseline: Moderate | 0 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Baseline: Severe | 0 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Week 24: None to minimal | 26 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Week 24: Moderate | 1 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores | Baseline: None to minimal | 29 participants |
Secondary
Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8)
The PHQ-8 is an eight item self-reported measure of depression. Each item is rated on a scale ranging from 0 (not at all) to 3 (nearly every day). Total score is the sum of individual eight items and ranges from 0 to 24, with higher scores indicating more severe depression symptoms. Total score of 0 to 5 indicates none to minimal depression, 6 to 10 indicates mild depression, 11 to 15 indicates moderate depression, 16 to 20 indicates moderately severe depression and 21 to 24 indicates severe depression.
Time frame: Baseline, Week 24
Population: FAS. Here Number Analyzed signifies those participants who were evaluated for this outcome at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Baseline: None to minimal | 27 participants |
| Placebo | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Baseline: Mild | 8 participants |
| Placebo | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Baseline: Moderate | 0 participants |
| Placebo | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Baseline: Moderately severe | 1 participants |
| Placebo | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Baseline: Severe | 0 participants |
| Placebo | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Week 24: None to minimal | 23 participants |
| Placebo | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Week 24: Mild | 8 participants |
| Placebo | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Week 24: Moderate | 1 participants |
| Placebo | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Week 24: Moderately severe | 1 participants |
| Placebo | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Week 24: Severe | 0 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Week 24: Moderate | 3 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Baseline: None to minimal | 28 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Week 24: None to minimal | 24 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Baseline: Mild | 5 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Week 24: Severe | 0 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Baseline: Moderate | 1 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Week 24: Mild | 3 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Baseline: Moderately severe | 0 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Week 24: Moderately severe | 0 participants |
| LUM/IVA | Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) | Baseline: Severe | 0 participants |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 28
Population: The Safety Set was defined as all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 35 participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 9 participants |
| LUM/IVA | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 30 participants |
| LUM/IVA | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 15 participants |
Secondary
Relative (Percent) Change From Baseline in BMI at Week 24
BMI was defined as weight in kg divided by height in m\^2.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Relative (Percent) Change From Baseline in BMI at Week 24 | 1.5 percent change |
| LUM/IVA | Relative (Percent) Change From Baseline in BMI at Week 24 | 2.5 percent change |
p-value: 0.390595% CI: [-1.2, 3.1]Mixed effects model for repeated measure
Secondary
Relative (Percent) Change From Baseline in Duration of Sleep Time at Week 24
Participants were provided with a wrist-worn actigraphy device which continuously collected data about sleep duration and quality.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Relative (Percent) Change From Baseline in Duration of Sleep Time at Week 24 | -5.7 percent change | Standard Deviation 12.3 |
| LUM/IVA | Relative (Percent) Change From Baseline in Duration of Sleep Time at Week 24 | 1.5 percent change | Standard Deviation 9.79 |
Secondary
Relative (Percent) Change From Baseline in Exercise Duration During CPET at Week 24
Exercise duration is defined as the time at the termination of CPET exercise minus the corresponding time when CPET starts for each CPET exercise.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Relative (Percent) Change From Baseline in Exercise Duration During CPET at Week 24 | 0.4 percent change |
| LUM/IVA | Relative (Percent) Change From Baseline in Exercise Duration During CPET at Week 24 | -2.8 percent change |
p-value: 0.189495% CI: [-8, 1.6]Mixed effects model for repeated measure
Secondary
Relative (Percent) Change From Baseline in Functional VO2 Gain at Week 24
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Relative (Percent) Change From Baseline in Functional VO2 Gain at Week 24 | 1.46 percent change |
| LUM/IVA | Relative (Percent) Change From Baseline in Functional VO2 Gain at Week 24 | -4.85 percent change |
p-value: 0.061395% CI: [-12.94, 0.31]Mixed effects model for repeated measure
Secondary
Relative (Percent) 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: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Relative (Percent) Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 | -5.4 percent change |
| LUM/IVA | Relative (Percent) Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 | -1.8 percent change |
p-value: 0.309195% CI: [-3.4, 10.4]Mixed effects model for repeated measure
Secondary
Relative (Percent) Change From Baseline in Physical Activity as Determined by Actigraphy at Week 24
Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily physical activities.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Relative (Percent) Change From Baseline in Physical Activity as Determined by Actigraphy at Week 24 | -5 percent change | Standard Deviation 26.9 |
| LUM/IVA | Relative (Percent) Change From Baseline in Physical Activity as Determined by Actigraphy at Week 24 | -7 percent change | Standard Deviation 24.3 |
Secondary
Relative (Percent) Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Relative (Percent) Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24 | 2.0 percent change |
| LUM/IVA | Relative (Percent) Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24 | 3.0 percent change |
p-value: 0.588995% CI: [-2.7, 4.7]Mixed effects model for repeated measure
Secondary
Relative (Percent) Change From Baseline in Time Above Sedentary Duration at Week 24
Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily activities and sleep duration and quality.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Relative (Percent) Change From Baseline in Time Above Sedentary Duration at Week 24 | 0.2 percent change | Standard Deviation 64.76 |
| LUM/IVA | Relative (Percent) Change From Baseline in Time Above Sedentary Duration at Week 24 | 2.3 percent change | Standard Deviation 77.18 |
Secondary
Relative (Percent) Change From Baseline in VO2 at Anaerobic Threshold at Week 24
Anaerobic threshold was defined as the exercise intensity at which lactate starts to accumulate.
Time frame: Baseline, Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Relative (Percent) Change From Baseline in VO2 at Anaerobic Threshold at Week 24 | 9.4 percent change |
| LUM/IVA | Relative (Percent) Change From Baseline in VO2 at Anaerobic Threshold at Week 24 | 1.8 percent change |
p-value: 0.223795% CI: [-19.8, 4.7]Mixed effects model for repeated measure