Pragmatic Open - Label Randomized Clinical Trial of FF/UMEC/VI vs Non-ellipta Usual Care ICS-LABA for Adult Participants With Uncontrolled Asthma

The ACQ-7 measures 7 attributes of asthma control and consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath, and wheeze) with response options ranging from 0 (no impairment/limitation) to 6 (total impairment/ limitation).ACQ-7 total score is the mean of the responses of the 7 items, ranges from 0 to 6. Higher score indicates poor control. A score of less than equal to (<=)0.75 indicates well-controlled asthma, a score of between 0.75 and 1.5 indicates partially controlled asthma, and a score >=1.5 indicates poorly controlled asthma. Greater than or equal to 0.5 point decrease from baseline suggests a clinically important change in asthma control. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention. Percentage values are rounded off.

The 4-point composite endpoint is defined as meeting the following criteria: Change from baseline in trough FEV1 >= 100 milliliter (mL) at Week 52, Controlled asthma based on ACQ-5 total score <= 1.5 at Week 52, No severe asthma exacerbations over 52 weeks and oral corticosteroids (OCS)-free over 52 weeks

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on treatment is defined as the last FEV1 value obtained prior to the morning dose of investigational product. Spirometry was performed to assess FEV1. Baseline is defined as the last acceptable/borderline acceptable pre-dose FEV1 obtained at the Randomization Visit (Visit 2/Day 1).

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on treatment is defined as the last FEV1 value obtained prior to the morning dose of investigational product. Spirometry was performed to assess FEV1. Baseline is defined as the last acceptable/borderline acceptable pre-dose FEV1 obtained at the Randomization Visit (Visit 2/Day 1). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 24) value. Percentage values are rounded-off.

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on treatment is defined as the last FEV1 value obtained prior to the morning dose of investigational product. Spirometry was performed to assess FEV1. Baseline is defined as the last acceptable/borderline acceptable pre-dose FEV1 obtained at the Randomization Visit (Visit 2/Day 1).

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on treatment is defined as the last FEV1 value obtained prior to the morning dose of investigational product. Spirometry was performed to assess FEV1. Baseline is defined as the last acceptable/borderline acceptable pre-dose FEV1 obtained at the Randomization Visit (Visit 2/Day 1). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 24) value. Percentage values are rounded-off.

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on treatment is defined as the last FEV1 value obtained prior to the morning dose of investigational product. Spirometry was performed to assess FEV1. Baseline is defined as the last acceptable/borderline acceptable pre-dose FEV1 obtained at the Randomization Visit (Visit 2/Day 1).

The ACQ-7 measures 7 attributes of asthma control and consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze) with response options ranging from zero (no impairment/limitation) to 6 (total impairment/ limitation). ACQ-7 total score is the mean of the responses of the 7 items, ranges from 0 to 6. Higher score indicates poor control. A score of less than equal to (<=) 0.75 indicates well-controlled asthma, a score of between 0.75 and 1.5 indicates partially controlled asthma, and a score >= 1.5 indicates poorly controlled asthma. Greater than or equal to 0.5 point decrease from baseline suggests a clinically important change in asthma control. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention.

The ACQ-6 is a shortened version of the ACQ-7 derived by removing one element (lung function element) from the original version. ACQ-6 consists of 6 questions scored from zero (no impairment/limitation) to six (total impairment/ limitation). Higher scores indicate greater impairment. Mean scores of <=0.75 indicate well-controlled asthma, scores between 0.75 and 1.5 indicate partially controlled asthma, and scores >=1.5 indicate poorly controlled asthma. A decrease in ACQ-6 score from Baseline indicates an improvement in asthma control, and individual changes of at least 0.5 are considered clinically meaningful. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention. Percentage values are rounded off.

The ACQ-6 is a shortened version of the ACQ-7 derived by removing one element (lung function element) from the original version. ACQ-6 consists of 6 questions scored from zero (no impairment/limitation) to six (total impairment/ limitation). Higher scores indicate greater impairment. Mean scores of <=0.75 indicate well-controlled asthma, scores between 0.75 and 1.5 indicate partially controlled asthma, and scores >=1.5 indicate poorly controlled asthma. A decrease in ACQ-6 score from Baseline indicates an improvement in asthma control, and individual changes of at least 0.5 are considered clinically meaningful. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention.

The ACQ-5 is a five-item questionnaire designed to be self-completed by the participants to assess the most common asthma symptoms. The 5 questions enquired to recall how their asthma had been during the previous week and to respond about the frequency and/or severity of symptoms (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze). The overall ACQ-5 response option is the mean score of all 5 questions representing 0=no impairment/limitation and 6=total impairment/ limitation. Higher scores indicated more limitations and lower scores indicated better asthma control. Higher score indicates worse symptoms. Greater than or equal to 0.5 point decrease from baseline suggests a clinically important change in asthma control. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention. Percentage values are rounded-off.

The ACQ-5 is a five-item questionnaire designed to be self-completed by the participants to assess the most common asthma symptoms. The 5 questions enquired to recall how their asthma had been during the previous week and to respond about the frequency and/or severity of symptoms (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze). The overall ACQ-5 response option is the mean score of all 5 questions representing 0=no impairment/limitation and 6=total impairment/ limitation. Higher scores indicated more limitations and lower scores with better asthma control. Higher score indicates worse symptoms. Greater than or equal to 0.5 point decrease from Baseline suggests a clinically important change in asthma control. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention.

The ACQ-7 measures 7 attributes of asthma control and consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath, and wheeze) with response options ranging from 0 (no impairment/limitation) to 6 (total impairment/ limitation). ACQ-7 total score is the mean of the responses of the 7 items, ranges from 0 to 6. Higher score indicates poor control. A score of less than equal to 0.75 indicates well-controlled asthma, a score of between 0.75 and 1.5 indicates partially controlled asthma, and a score >=1.5 indicates poorly controlled asthma. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 24) value

The ACQ-7 measures 7 attributes of asthma control and consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath, and wheeze) with response options ranging from 0 (no impairment/limitation) to 6 (total impairment/ limitation). ACQ-7 total score is the mean of the responses of the 7 items, ranges from 0 to 6. Higher score indicates poor control. A score of less than equal to 0.75 indicates well-controlled asthma, a score of between 0.75 and 1.5 indicates partially controlled asthma, and a score >=1.5 indicates poorly controlled asthma. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention.

The ACQ-6 is a shortened version of the ACQ-7 derived by removing one element (lung function element) from the original version. ACQ-6 consists of 6 questions scored from zero (no impairment/limitation) to six (total impairment/ limitation). Higher scores indicate greater impairment. Mean scores of <=0.75 indicate well-controlled asthma, scores between 0.75 and 1.5 indicate partially controlled asthma, and scores >=1.5 indicate poorly controlled asthma. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 24) value.

The ACQ-6 is a shortened version of the ACQ-7 derived by removing one element (lung function element) from the original version. ACQ-6 consists of 6 questions scored from zero (no impairment/limitation) to six (total impairment/ limitation). Higher scores indicate greater impairment. Mean scores of <=0.75 indicate well-controlled asthma, scores between 0.75 and 1.5 indicate partially controlled asthma, and scores >=1.5 indicate poorly controlled asthma. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention.

The ACQ-5 is a five-item questionnaire designed to be self-completed by the participants to assess the most common asthma symptoms. The 5 questions enquired to recall how their asthma had been during the previous week and to respond about the frequency and/or severity of symptoms (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze). The overall ACQ-5 response option is the mean score of all 5 questions representing 0=no impairment/limitation and 6=total impairment/limitation. Higher scores indicated more limitations and lower scores indicated better asthma control. Higher score indicates worse symptoms. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 24) value.

The ACQ-5 is a five-item questionnaire designed to be self-completed by the participants to assess the most common asthma symptoms. The 5 questions enquired to recall how their asthma had been during the previous week and to respond about the frequency and/or severity of symptoms (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze). The overall ACQ-5 response option is the mean score of all 5 questions representing 0=no impairment/limitation and 6=total impairment/limitation. Higher scores indicated more limitations and lower scores indicated better asthma control. Higher score indicates worse symptoms. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention.

The ACT is a validated self-completed questionnaire utilizing 5 questions to assess asthma control on a 5-point categorical scale ranging from 1 (not controlled at all) to 5 (completely controlled) with higher scores indicating better control. Total ACT score is calculated as the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 15 suggests that the participant's asthma is poorly controlled, a score of 16 to 19 suggests that the participant's asthma is somewhat controlled, and a score of 20 to 25 suggests that the participant's asthma is well controlled. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention. CFB was calculated by subtracting Baseline value from the post-dose visit (Week 24) value.

The ACT is a validated self-completed questionnaire utilizing 5 questions to assess asthma control on a 5-point categorical scale ranging from 1 (not controlled at all) to 5 (completely controlled) with higher scores indicating better control. Total ACT score is calculated as the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 15 suggests that the participant's asthma is poorly controlled, a score of 16-to 19 suggests that the participant's asthma is somewhat controlled, and a score of 20 to 25 suggests that the participant's asthma is well controlled. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention.

The 4-point composite endpoint is defined as meeting the following criteria: 1. Change from baseline in trough FEV1 ≥ 100 mL at Week 52; 2. Controlled asthma based on ACQ-5 total score <= 1.5 at Week 52; 3. No severe asthma exacerbations over 52 weeks; 4. OCS-free over 52 weeks. Subset on participants receiving ICS/LABA prior to randomization.

The 4-point composite endpoint is defined as meeting the following criteria: 1. Change from baseline in trough FEV1 ≥ 100 mL at Week 52; 2. Controlled asthma based on ACQ-5 total score <= 1.5 at Week 52; 3. No severe asthma exacerbations over 52 weeks; 4. OCS-free over 52 weeks. Subset on participants receiving no treatment prior to randomization (no ICS-containing therapy within the 3 months prior to randomization).

AQLQ-12 is a disease-specific, self-administered quality of life questionnaire used to evaluate impact of asthma treatments on quality of life of asthma sufferers. AQLQ-12 has 32 items in 4 domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items), environmental stimuli (4 items). For 32 items on questionnaire, response format consists of a 7-point scale, where 1 indicates "total impairment" and 7 indicates "no impairment." AQLQ-12 total score is defined as average of scores from all 32 questions; thus, total score ranges from 1="total impairment" to 7=indicates "no impairment". Higher score is better asthma-related health-related quality of life. Baseline is last non-missing value prior to or on prescription date of study intervention. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 24) value.

AQLQ-12 is a disease-specific, self-administered quality of life questionnaire to evaluate impact of asthma treatments on quality of life of asthma sufferers. AQLQ-12 has 32 items in 4 domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items), environmental stimuli (4 items). For 32 items on questionnaire, response format consists of a 7-point scale, where a value of 1 indicates "total impairment" and a value of 7 indicates "no impairment." AQLQ-12 total score is defined as average of scores from all 32 questions; thus, total score ranges from 1="total impairment" to 7="no impairment". Higher score is better asthma-related health-related quality of life. Baseline is last non-missing value prior to or on prescription date of study intervention.

AQLQ-12 is a disease-specific, self-administered quality of life questionnaire used to evaluate impact of asthma treatments on quality of life of asthma sufferers. AQLQ-12 has 32 items in 4 domains: symptoms (12 items), environmental stimuli (4 items), activity limitation (11 items), emotional function (5 items). For 32 items on questionnaire, response format consists of a 7-point scale, where 1 indicates "total impairment" and 7 indicates "no impairment." AQLQ-12 each domain score total score is defined as average of scores from all the 32 questions from the respective domain; thus, each domain total score ranges from 1="total impairment" to 7=indicates "no impairment". Higher score is better asthma-related health-related quality of life. Each domain score is the mean of item scores within that domain. Baseline is last non-missing value prior to or on prescription date of study intervention. CFB was calculated by subtracting Baseline value from the post-dose visit (Week 24) value.

AQLQ-12 is a disease-specific, self-administered quality of life questionnaire used to evaluate impact of asthma treatments on quality of life of asthma sufferers. AQLQ-12 has 32 items in 4 domains: symptoms (12 items), environmental stimuli (4 items), activity limitation (11 items), emotional function (5 items). For 32 items on questionnaire, response format consists of a 7-point scale, where 1 indicates "total impairment" and 7 indicates "no impairment." AQLQ-12 each domain score total score is defined as average of scores from all the 32 questions from the respective domain; thus, each domain total score ranges from 1="total impairment" to 7=indicates "no impairment". Higher score is better asthma-related health-related quality of life. Each domain score is the mean of item scores within that domain. Baseline is last non-missing value prior to or on prescription date of study intervention.

WPAI questionnaire measures impact due to poor health due to asthma on work and regular activities, yielding 4 percentage-based impairment scores, each ranges from 0 to 100%. Higher values=greater impairment and less productivity. Calculation of these 4 scores are as follows: 1. Work time missed due to health (Absenteeism)=hours missed due to health divided by (hours missed due to health+hours missed for other reasons+hours actually worked) *100. 2. Impairment while working due to health (Presenteeism) =Question (Q)5 score (from 0 to 10) divided by 10*100. 3. Overall work impairment due to health =Absenteeism+(1-Absenteeism fraction)*Presenteeism. 4. Activity impairment due to health =Q6 score (from 0 to 10) divided by 10*100. Baseline is last non-missing value prior to or on prescription date of study intervention. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 24) value.

WPAI questionnaire measures impact due to poor health due to asthma on work and regular activities, yielding 4 percentage-based impairment scores, each ranges from 0 to 100%. Higher value=greater impairment and less productivity. Calculation of these 4 scores are as follows: 1. Work time missed due to health (Absenteeism) =hours missed due to health divided by (hours missed due to health+hours missed for other reasons+hours actually worked) *100. 2. Impairment while working due to health (Presenteeism) =Question (Q)5 score (from 0 to 10) divided by 10*100. 3. Overall work impairment due to health =Absenteeism+(1-Absenteeism fraction)*Presenteeism. 4. Activity impairment due to health =Q6 score (from 0 to 10) divided by 10*100. Baseline is last non-missing value prior to or on prescription date of study intervention.

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on treatment is defined as the last FEV1 value obtained prior to the morning dose of investigational product. Spirometry was performed to assess FEV1. Baseline is defined as the last acceptable/borderline acceptable pre-dose FEV1 obtained at the Randomization Visit (Visit 2/Day 1). Per Protocol the study's subgroup analysis design, the analysis for this endpoint at Week 24 will be performed based on results from the composite (optimized) endpoint's Week 52 analysis. The pending results are expected to be available within 12 months of End of Study (EOS) date.

The ACQ-7 measures 7 attributes of asthma control \& includes 5 symptom questions (nocturnal awakening,symptoms on waking in morning,activity limitation,shortness of breath \& wheeze). Responses ranges from 0 (no impairment/limitation) to 6 (total impairment/ limitation). ACQ-7 total score is mean of the responses of 7 items, ranges from 0 to 6. Higher score = poor control. A score of <= 0.75 is well-controlled asthma; a score between 0.75 and 1.5 is partially controlled asthma \& a score >= 1.5 is poorly controlled asthma. >= 0.5 point decrease from baseline is clinically important change in asthma control. Baseline is last non-missing value prior to or on the prescription date of study intervention. Per Protocol study's subgroup analysis design, analysis for this endpoint at Week 24 will be performed based on results from composite (optimized) endpoint's Week 52 analysis. The pending results are expected to be available within 12 months of EOS date.

The ACQ-7 measures 7 attributes of asthma control \& includes 5 symptom questions (nocturnal awakening,symptoms on waking in the morning,activity limitation,shortness of breath \& wheeze). Responses ranges from 0 (no impairment/limitation) to 6 (total impairment/ limitation). ACQ-7 total score is mean of the responses of the 7 items, ranges from 0 to 6. Higher score = poor control. A score of <= 0.75 is well-controlled asthma; a score between 0.75 and 1.5 is partially controlled asthma \& a score >= 1.5 is poorly controlled asthma. >= 0.5 point decrease from baseline is clinically important change in asthma control. Baseline is last non-missing value prior to or on the prescription date of study intervention.

The ACQ-7 measures 7 attributes of asthma control and consists of 5 symptom related questions with response options ranging from 0 (no impairment/limitation) to 6 (total impairment/ limitation). ACQ-7 total score is mean of responses of the 7 items, ranges from 0 to 6. Higher score indicates poor control. A score of less than equal to 0.75 indicates well-controlled asthma, a score between 0.75 and 1.5 indicates partially controlled asthma, and a score >=1.5 indicates poorly controlled asthma. Baseline is defined as last non-missing value prior to or on prescription date of study intervention. Per Protocol the study's subgroup analysis design, the analysis for this endpoint at Week 24 will be performed based on results from the composite (optimized) endpoint's Week 52 analysis. The pending results are expected to be available within 12 months of End of Study date.

The ACQ-7 measures 7 attributes of asthma control and consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath, and wheeze) with response options ranging from 0 (no impairment/limitation) to 6 (total impairment/ limitation). ACQ-7 total score is the mean of the responses of the 7 items, ranges from 0 to 6. Higher score indicates poor control. A score of less than equal to 0.75 indicates well-controlled asthma, a score between 0.75 and 1.5 indicates partially controlled asthma, and a score >=1.5 indicates poorly controlled asthma. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention.

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on treatment is defined as the last FEV1 value obtained prior to the morning dose of investigational product. Spirometry was performed to assess FEV1. Baseline is defined as the last acceptable/borderline acceptable pre-dose FEV1 obtained at the Randomization Visit (Visit 2/Day 1). Per Protocol the study's subgroup analysis design, the analysis for this endpoint at Week 24 will be performed based on results from the composite (optimized) endpoint's Week 52 analysis. The pending results are expected to be available within 12 months of End of Study date.

The ACQ-7 measures 7 attributes of asthma control and consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze) with response options ranging from zero (no impairment/limitation) to 6 (total impairment/ limitation). A score of <=0.75 indicates well-controlled asthma and a score >=1.5 indicates poorly controlled asthma. >= 0.5 point decrease from baseline is clinically important change in asthma control. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention. Per Protocol the study's subgroup analysis design, the analysis for this endpoint at Week 24 will be performed based on results from the composite (optimized) endpoint's Week 52 analysis. The pending results are expected to be available within 12 months of End of Study date.

The ACQ-7 measures 7 attributes of asthma control and consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze). Response ranges from 0 (no impairment/limitation) to 6 (total impairment/ limitation). ACQ-7 total score is mean of the responses of 7 items, ranges from 0 to 6. Higher score = poor control. A score of <=0.75 indicates is well-controlled asthma; and a score >=1.5 indicates poorly controlled asthma. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention.

The ACQ-7 measures 7 attributes of asthma control and consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze) with response options ranging from zero (no impairment/limitation) to 6 (total impairment/ limitation). A score of less than equal to 0.75 indicates well-controlled asthma, a score between 0.75 and 1.5 indicates partially controlled asthma, and a score >=1.5 indicates poorly controlled asthma. A change of 0.5 in score suggests a clinically important change in asthma control. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention. Per Protocol the study's subgroup analysis design, the analysis for this endpoint at Week 24 will be performed based on results from the composite (optimized) endpoint's Week 52 analysis. The pending results are expected to be available within 12 months of End of Study date.

The ACQ-7 measures 7 attributes of asthma control and consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze) with response options ranging from zero (no impairment/limitation) to 6 (total impairment/ limitation). A score of less than equal to 0.75 indicates well-controlled asthma, a score of between 0.75 and 1.5 indicates partially controlled asthma, and a score >=1.5 indicates poorly controlled asthma. Baseline is defined as the last non-missing value prior to or on the prescription date of study intervention.