Asthma
Conditions
Keywords
QVM149, Asthma, Moderate Asthma, Severe Asthma, ICS/LABA/LAMA, ICS/LABA, LAMA, Adult
Brief summary
The purpose of this trial was to demonstrate that the efficacy of two treatment arms of the fixed-dose combination product QVM149 was non-inferior to the efficacy of the free combination arm of salmeterol/ fluticasone+ tiotropium in uncontrolled moderate to severe asthmatic patients. The planned duration of treatment in this study was 24 weeks, followed up by a 7-day follow-up period.
Detailed description
This study used a randomized, partially-blinded, 24-week, parallel-group, non-inferiority, open-label active controlled design. The study was partially open-label. Investigators and patients had knowledge of treatment allocation between QVM149 and/or comparator, however the QVM149 strength allocation was masked. The global sponsor team responsible for data review and analysis was blinded to all treatment allocations The study consisted of a screening period of up to 1-week, run-in period of 2-weeks, randomized treatment period of 24-weeks, and a follow-up period of 1-week. At the screening visit, informed consent was obtained, and current and prohibited medications were reviewed. Rescue medication was provided to all patients who met the eligibility criteria and was to be used on an as needed basis throughout the study. At the run-in visit, inclusion and exclusion criteria were reviewed and the patients were supplied with open-label long acting β2-adrenergic agonist/inhaled corticosteroids (LABA/ICS) salmeterol/fluticasone 50/250 μg b.i.d or 50/500 μg b.i.d to match their ICS background medication dose to be stopped at randomization visit. All patients who met the eligibility criteria were randomized to 1 of 3 treatment arms with a randomization ratio of 1:1:1. The patients were stratified at randomization according to the ICS dose component of background ICS/LABA (medium or high dose) and region. Treatment period visits were scheduled every 8 weeks. The study used two doses of QVM149 (high dose \[150/50/160 μg\] and a medium dose \[150/50/80 μg\] o.d. delivered via Concept1 inhaler) and a comparator treatment (salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d delivered via Respimat®). All randomized patients were contacted (by telephone) 7 days following the last dose of study medication or last visit, whichever was later, for Safety Follow-up visit.
Interventions
DRUGQVM149
Indacaterol acetate / glycopyrronium bromide / mometasone furoate
DRUGSalmeterol/fluticasone plus tiotropium
Free triple arm of salmeterol / fluticasone plus tiotropium
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The free triple combination of salmeterol/fluticasone + tiotropium was open label, for which investigators and patients had full knowledge that the patient had been assigned free triple combination comparator treatment. Within the two QVM149 treatment arms patients, investigator staff, and persons performing the assessments, remained blind to the identity of the actual QVM149 treatment dose but had full knowledge that the patient had been assigned QVM149 as study treatment. The data analysts and sponsor team were blinded to Case Report Forms that reveal the treatment arm. Randomization data and treatment codes were kept strictly confidential until the time of unblinding, and was not accessible by anyone else involved in the study.
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a diagnosis of asthma for a period of at least 6 months prior to Visit 1 with current asthma severity ≥ step 4 (GINA 2017). * Patients who had used ICS/LABA combinations for asthma for at least 3 months and at stable medium or high dose of ICS/LABA for at least 1 month prior to Visit 1. * Patients were required to be symptomatic at screening despite treatment with medium or high stable doses of ICS/LABA as defined by ACQ-7 score ≥ 1.5 at visits 101 and 201 (randomization visit). * Patients with history of at least one severe asthma exacerbation which required medical care from a physician, emergency room visit (or local equivalent structure) or hospitalization in the 12 months prior to Visit 1 and required systemic corticosteroid treatment for at least 3 days including physician guided self-management treatment with oral corticosteroids as part of written asthma action plan. * Pre-bronchodilator FEV1 of \< 85 % of the predicted normal value for the patient after withholding bronchodilators prior to spirometry at both Visit 101 and Visit 201. * Patients who demonstrated an increase in FEV1 of ≥ 12% and 200 ml.
Exclusion criteria
* Patients who had a smoking history of greater than 20 pack years. * Patients diagnosed with Chronic Obstructive Pulmonary Disease (COPD). * Patients who had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening). * Patients treated with a LAMA for asthma within 3 months prior to Visit 1. * Patients who had a respiratory tract infection or clinical significant asthma worsening as defined by Investigator within 4 weeks prior to Visit 1 or between Visit 1 and Visit 201.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score | Baseline and Week 24 | The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional funtion, and emotional stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score | Baseline, Week 16 and Week 24 | The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. Higher score indicates worst symptoms. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function. |
| Change From Baseline in AQLQ Total Score | Baseline and Week 16 | The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional function and environmental stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life. |
| Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Decrease From Baseline ACQ-7 ≥ 0.5 | Baseline and Week 24 | The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. Higher score indicates worst symptoms. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function. Decrease of ACQ-7 score of at least 0.5 from baseline was considered clinically meaningful. |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) | Baseline, Week 8, Week 16 and Week 24 | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Trough FEV1 is the mean of two FEV1 values measures taken 15 minutes (min) and 45 min prior to evening dose. |
| Change From Baseline in Forced Vital Capacity (FVC) | Baseline, Week 8, Week 16 and Week 24 | FVC is the total volume of air exhaled during a expiratory maneuvre. It was assessed by performing a spirometry assessment. |
| Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) | Baseline, Week 8, Week 16 and Week 24 | Forced expiratory flow during the mid (25 - 75%) portion of the FVC. It was assessed by performing spirometric assessment. |
| Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Change From Baseline AQLQ ≥ 0.5 | Baseline and Week 24 | The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional function and environmental stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life. An improvement of 0.5 points in AQLQ score is considered to be the minimally clinically important difference in asthma. |
Countries
Argentina, Chile, Colombia, Czechia, Germany, Greece, Hungary, India, Israel, Mexico, Peru, Poland, Russia, Serbia, Slovakia, South Africa, Spain, Taiwan, Turkey (Türkiye), Vietnam
Participant flow
Recruitment details
Participants took part in 166 investigative sites in 20 countries from 05 Feb 2018 to 19 Jul 2019.
Pre-assignment details
A total of 1917 participants were screened. A 2 week run-in phase preceded the randomized treatment phase of the study. 1821 participants entered the run-in phase. Those participants who met the inclusion criteria entered the randomized treatment phase. Participants were randomized with a randomization ratio of 1:1:1 to three treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| QVM149 150/50/80 μg QVM149 150/50/80 μg o.d. delivered via Concept1 | 474 |
| QVM149 150/50/160 μg QVM149 150/50/160 μg o.d. delivered via Concept1 | 476 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat® | 476 |
| Total | 1,426 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 | 3 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 |
| Overall Study | Physician Decision | 2 | 3 | 7 |
| Overall Study | Pregnancy | 0 | 2 | 0 |
| Overall Study | Randomized in error | 0 | 0 | 1 |
| Overall Study | Sponsor decision | 1 | 0 | 0 |
| Overall Study | Subject/Guardian Decision | 10 | 6 | 11 |
| Overall Study | Techinical Problems | 3 | 1 | 5 |
Baseline characteristics
| Characteristic | QVM149 150/50/80 μg | QVM149 150/50/160 μg | Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Total |
|---|---|---|---|---|
| Age, Continuous | 51.9 Years STANDARD_DEVIATION 13.58 | 52.7 Years STANDARD_DEVIATION 13.34 | 53.1 Years STANDARD_DEVIATION 13.08 | 52.5 Years STANDARD_DEVIATION 13.33 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 5 Participants | 1 Participants | 10 Participants | 16 Participants |
| Race/Ethnicity, Customized Asian | 36 Participants | 34 Participants | 33 Participants | 103 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 5 Participants | 3 Participants | 14 Participants |
| Race/Ethnicity, Customized Other | 26 Participants | 44 Participants | 39 Participants | 109 Participants |
| Race/Ethnicity, Customized White | 401 Participants | 392 Participants | 391 Participants | 1184 Participants |
| Sex: Female, Male Female | 306 Participants | 289 Participants | 307 Participants | 902 Participants |
| Sex: Female, Male Male | 168 Participants | 187 Participants | 169 Participants | 524 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 474 | 0 / 476 | 1 / 475 |
| other Total, other adverse events | 245 / 474 | 246 / 476 | 241 / 475 |
| serious Total, serious adverse events | 14 / 474 | 18 / 476 | 19 / 475 |
Outcome results
Primary
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score
The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional funtion, and emotional stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life.
Time frame: Baseline and Week 24
Population: Analysis population included FAS with evaluable AQLQ data at both timepoints. No imputation was used for missing questions or missing total AQLQ score for this analysis. The analysis was performed on observed data only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVM149 150/50/80 μg | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score | 0.715 Score on a scale | Standard Error 0.07 |
| QVM149 150/50/160 μg | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score | 0.827 Score on a scale | Standard Error 0.069 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score | 0.753 Score on a scale | Standard Error 0.069 |
p-value: <0.001Mixed Model for Repeated Measures (MMRM)
p-value: <0.001MMRM
Secondary
Change From Baseline in AQLQ Total Score
The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional function and environmental stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life.
Time frame: Baseline and Week 16
Population: Analysis population included FAS with evaluable AQLQ data at both timepoints. No imputation was used for missing questions or missing total AQLQ score for this analysis. The analysis was performed on observed data only
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVM149 150/50/80 μg | Change From Baseline in AQLQ Total Score | 0.690 Score on a scale | Standard Error 0.069 |
| QVM149 150/50/160 μg | Change From Baseline in AQLQ Total Score | 0.755 Score on a scale | Standard Error 0.068 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in AQLQ Total Score | 0.673 Score on a scale | Standard Error 0.069 |
p-value: 0.71995% CI: [-0.079, 0.115]MMRM
p-value: 0.09795% CI: [-0.015, 0.179]MMRM
Secondary
Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score
The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. Higher score indicates worst symptoms. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function.
Time frame: Baseline, Week 16 and Week 24
Population: Analysis population included FAS with ACQ-7 data at the respective visit. Number analyzed signified number of participants who were evaluable for this measure at specified timepoints. No imputation was used for missing questions or missing total ACQ-7 score for this analysis. The analysis was performed on observed data only
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVM149 150/50/80 μg | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score | Week 16 | -1.043 Score on a scale | Standard Error 0.045 |
| QVM149 150/50/80 μg | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score | Week 24 | -1.080 Score on a scale | Standard Error 0.046 |
| QVM149 150/50/160 μg | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score | Week 16 | -1.098 Score on a scale | Standard Error 0.045 |
| QVM149 150/50/160 μg | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score | Week 24 | -1.172 Score on a scale | Standard Error 0.045 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score | Week 16 | -1.020 Score on a scale | Standard Error 0.045 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score | Week 24 | -1.048 Score on a scale | Standard Error 0.046 |
Comparison: Week 16p-value: 0.30895% CI: [-0.113, 0.067]MMRM
Comparison: Week 16p-value: 0.04495% CI: [-0.169, 0.012]MMRM
Comparison: Week 24p-value: 0.24595% CI: [-0.125, 0.06]MMRM
Comparison: Week 24p-value: 0.00495% CI: [-0.216, -0.032]MMRM
Secondary
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75)
Forced expiratory flow during the mid (25 - 75%) portion of the FVC. It was assessed by performing spirometric assessment.
Time frame: Baseline, Week 8, Week 16 and Week 24
Population: Analysis population included FAS with FEF25-75 data at the respective visit. Number analyzed signified number of participants who were evaluable for this measure at specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVM149 150/50/80 μg | Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) | Week 8 | 0.290 Litres/second (L/s) | Standard Error 0.027 |
| QVM149 150/50/80 μg | Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) | Week 16 | 0.291 Litres/second (L/s) | Standard Error 0.028 |
| QVM149 150/50/80 μg | Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) | Week 24 | 0.290 Litres/second (L/s) | Standard Error 0.028 |
| QVM149 150/50/160 μg | Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) | Week 24 | 0.375 Litres/second (L/s) | Standard Error 0.028 |
| QVM149 150/50/160 μg | Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) | Week 8 | 0.332 Litres/second (L/s) | Standard Error 0.027 |
| QVM149 150/50/160 μg | Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) | Week 16 | 0.355 Litres/second (L/s) | Standard Error 0.027 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) | Week 24 | 0.286 Litres/second (L/s) | Standard Error 0.028 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) | Week 8 | 0.270 Litres/second (L/s) | Standard Error 0.027 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) | Week 16 | 0.297 Litres/second (L/s) | Standard Error 0.027 |
Comparison: Week 8p-value: 0.56395% CI: [-0.048, 0.087]MMRM
Comparison: Week 8p-value: 0.06895% CI: [-0.005, 0.129]MMRM
Comparison: Week 16p-value: 0.84495% CI: [-0.076, 0.062]MMRM
Comparison: Week 16p-value: 0.09795% CI: [-0.01, 0.125]MMRM
Comparison: Week 24p-value: 0.92795% CI: [-0.067, 0.074]MMRM
Comparison: Week 24p-value: 0.01395% CI: [0.019, 0.159]MMRM
Secondary
Change From Baseline in Forced Vital Capacity (FVC)
FVC is the total volume of air exhaled during a expiratory maneuvre. It was assessed by performing a spirometry assessment.
Time frame: Baseline, Week 8, Week 16 and Week 24
Population: Analysis population included FAS with FVC data at the respective visit. Number analyzed signified number of participants who were evaluable for this measure at specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVM149 150/50/80 μg | Change From Baseline in Forced Vital Capacity (FVC) | Week 16 | 0.221 Litre (L) | Standard Error 0.021 |
| QVM149 150/50/80 μg | Change From Baseline in Forced Vital Capacity (FVC) | Week 8 | 0.216 Litre (L) | Standard Error 0.021 |
| QVM149 150/50/80 μg | Change From Baseline in Forced Vital Capacity (FVC) | Week 24 | 0.214 Litre (L) | Standard Error 0.022 |
| QVM149 150/50/160 μg | Change From Baseline in Forced Vital Capacity (FVC) | Week 16 | 0.275 Litre (L) | Standard Error 0.021 |
| QVM149 150/50/160 μg | Change From Baseline in Forced Vital Capacity (FVC) | Week 8 | 0.272 Litre (L) | Standard Error 0.021 |
| QVM149 150/50/160 μg | Change From Baseline in Forced Vital Capacity (FVC) | Week 24 | 0.280 Litre (L) | Standard Error 0.022 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in Forced Vital Capacity (FVC) | Week 8 | 0.219 Litre (L) | Standard Error 0.021 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in Forced Vital Capacity (FVC) | Week 24 | 0.186 Litre (L) | Standard Error 0.022 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in Forced Vital Capacity (FVC) | Week 16 | 0.217 Litre (L) | Standard Error 0.021 |
Comparison: Week 16p-value: 0.02895% CI: [0.006, 0.109]MMRM
Comparison: Week 8p-value: 0.90895% CI: [-0.055, 0.049]MMRM
Comparison: Week 8p-value: 0.04695% CI: [0.001, 0.104]MMRM
Comparison: Week 16p-value: 0.8795% CI: [-0.047, 0.056]MMRM
Comparison: Week 24p-value: 0.30395% CI: [-0.026, 0.083]MMRM
Comparison: Week 24p-value: <0.00195% CI: [0.041, 0.148]MMRM
Secondary
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Trough FEV1 is the mean of two FEV1 values measures taken 15 minutes (min) and 45 min prior to evening dose.
Time frame: Baseline, Week 8, Week 16 and Week 24
Population: Analysis population included FAS with FEV1 data at the respective visit. Number analyzed signified number of participants who were evaluable for this outcome measure at specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVM149 150/50/80 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) | Week 16 | 0.251 Litre (L) | Standard Error 0.02 |
| QVM149 150/50/80 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) | Week 8 | 0.246 Litre (L) | Standard Error 0.02 |
| QVM149 150/50/80 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) | Week 24 | 0.248 Litre (L) | Standard Error 0.021 |
| QVM149 150/50/160 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) | Week 16 | 0.319 Litre (L) | Standard Error 0.02 |
| QVM149 150/50/160 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) | Week 8 | 0.309 Litre (L) | Standard Error 0.02 |
| QVM149 150/50/160 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) | Week 24 | 0.334 Litre (L) | Standard Error 0.021 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) | Week 8 | 0.243 Litre (L) | Standard Error 0.02 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) | Week 24 | 0.238 Litre (L) | Standard Error 0.021 |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) | Week 16 | 0.253 Litre (L) | Standard Error 0.02 |
Comparison: Week 8p-value: 0.89295% CI: [-0.046, 0.052]MMRM
Comparison: Week 8p-value: 0.00795% CI: [0.018, 0.115]MMRM
Comparison: Week 16p-value: 0.94595% CI: [-0.05, 0.047]MMRM
Comparison: Week 16p-value: 0.00795% CI: [0.018, 0.114]MMRM
Comparison: Week 24p-value: 0.71395% CI: [-0.041, 0.06]MMRM
Comparison: Week 24p-value: <0.00195% CI: [0.046, 0.146]MMRM
Secondary
Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Change From Baseline AQLQ ≥ 0.5
The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional function and environmental stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life. An improvement of 0.5 points in AQLQ score is considered to be the minimally clinically important difference in asthma.
Time frame: Baseline and Week 24
Population: Analysis population included FAS with evaluable AQLQ data at both timepoints. Missing data imputation was used to perform this analysis. Subjects with missing values were imputed as non-responders (a non-responder was defined as \<0.5 increase in AQLQ score at week 24)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| QVM149 150/50/80 μg | Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Change From Baseline AQLQ ≥ 0.5 | 318 Participants |
| QVM149 150/50/160 μg | Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Change From Baseline AQLQ ≥ 0.5 | 333 Participants |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Change From Baseline AQLQ ≥ 0.5 | 299 Participants |
p-value: 0.10895% CI: [0.91, 1.49]Regression, Logistic
p-value: 0.01395% CI: [1.03, 1.7]Regression, Logistic
Secondary
Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Decrease From Baseline ACQ-7 ≥ 0.5
The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. Higher score indicates worst symptoms. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function. Decrease of ACQ-7 score of at least 0.5 from baseline was considered clinically meaningful.
Time frame: Baseline and Week 24
Population: Analysis population included FAS with evaluable ACQ-7 data at both timepoints. Missing data imputation was used to perform this analysis. Subjects with missing values were imputed as non-responders (a non-responder was defined as \<0.5 decrease in ACQ-7 score at week 24)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| QVM149 150/50/80 μg | Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Decrease From Baseline ACQ-7 ≥ 0.5 | 393 Participants |
| QVM149 150/50/160 μg | Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Decrease From Baseline ACQ-7 ≥ 0.5 | 387 Participants |
| Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg | Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Decrease From Baseline ACQ-7 ≥ 0.5 | 375 Participants |
p-value: 0.06195% CI: [0.94, 1.61]Regression, Logistic
p-value: 0.22795% CI: [0.85, 1.46]Regression, Logistic