Asthma
Conditions
Keywords
Metered-dose inhaler (MDI), Leukotriene receptor agonist (LTRA), Inhaled corticosteroid (ICS), Short -acting β2agonist (SABA)
Brief summary
This is a US study comparing the efficacy and safety of BDA MDI \[Budesonide/Albuterol Sulfate (BDA) metered dose inhaler (MDI)\] with AS \[Albuterol Sulfate\] MDI, both are administered as needed for up to 12 months.
Detailed description
This is a phase IIIb, multicenter, randomized, double-blind, parallel-group, event-driven, variable-length, decentralized study. Participants from around 40 to 50 centers located in the US will be screened and randomized 1:1 to receive one of the following two treatments to be used as needed: BDA MDI (160/180 μg) and AS MDI (180 μg). Participants 12 years of age and older with asthma will be recruited with all visits conducted virtually. Eligible participants must be using as-needed SABA (Short -acting β2agonist) alone, or as-needed SABA on a background of either low-dose ICS (Inhaled corticosteroid) or a LTRA (Leukotriene receptor agonist), for the treatment of asthma. Participants will be stratified by pre-study asthma medication (SABA only, low-dose ICS + SABA and LTRA + SABA) and number of prior severe exacerbations (0, ≥1) in the 12 months prior to the Screening visit.
Interventions
DRUGBDA MDI
Participants will receive Budesonide and Albuterol Sulfate MDI 80/90 μg per Actuation 1 to 6 doses (2 inhalations/dose) per day as needed via Oral inhalation route.
DRUGAS MDI
Participants will receive Albuterol Sulfate MDI 90 μg per Actuation 1 to 6 doses (2 inhalations/dose) per day as needed via Oral inhalation route.
Sponsors
Parexel
Bond Avillion 2 Development LP
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant must be ≥12 years of age, at the time of signing the electronic informed consent form (eICF). For participants from 12 years of age to age of majority, their parents/legal guardian must provide signed consent, as appropriate, and participants will sign an assent form. 2. Diagnosis of asthma by a prescribing healthcare professional. Protocol-specified documentation of asthma diagnosis is required to confirm diagnosis of asthma. 3. Participants actively using SABA alone or SABA on a background of either low-dose ICS or LTRA. 4. Self-reported use of a SABA on ≥2 occasions, in response to symptoms (ie, not for exercise prophylaxis only), in the previous 2 weeks prior to enrollment. 5. An Asthma Impairment and Risk Questionnaire (AIRQ) score of ≥2 at Screening (Visit1/re-screen) and Randomisation (Randomization (Visit2) where applicable. Note, where screening Visit1/re-screen and randomization occur on the same day, AIRQ will only be completed once. 6. Females of child-bearing potential must have a negative pregnancy test prior to randomization and agree to use an acceptable method of contraception throughout the study. 7. Male participants who are in heterosexual relationships must be surgically sterile or agree to use an effective method of contraception (condom) if the female partner does not use contraception from the date the eICF is signed until 2 weeks after their last dose.
Exclusion criteria
1. Any evidence of significant lung disease other than asthma, such as chronic obstructive pulmonary disease, emphysema, idiopathic pulmonary fibrosis, sarcoidosis etc or any other significant disease (like malignancies or severe chronic diseases) that by Investigator judgment would interfere with the participant being able to comply with study procedures or complete the study. 2. Hospitalization due to asthma in the 3 months prior to enrollment or self-reported admission to the Intensive Care Unit with life-threatening asthma at any time in the past 3. Self-reported use of inhaled Long-Acting Beta-Agonists (LABA), theophylline, inhaled anticholinergic agent, cromone or medium/high dose ICS daily, as regular maintenance asthma therapy in the 3 months prior to enrollment 4. Self-reported use of systemic corticosteroids (SCS) for the treatment of asthma and any other condition in the 6 weeks prior to enrollment 5. Participants with a home supply of oral corticosteroids (OCS) to be used in the case of an asthma exacerbation or any other condition that could require a course of OCS, who are not willing to commit to the treating physician to stop using this medication for the duration of the study. 6. Receipt of any marketed (eg, omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab) or investigational biologic for the treatment of asthma at any time in the past 7. Receipt of bronchothermoplasty 8. Use of a SABA prophylactically primarily to prevent exercise induced bronchospasm (EIB) and not to treat symptoms 9. Currently receiving systemic treatment with potent cytochrome P3A4 inhibitors (eg, ketoconazole, itraconazole, and ritonavir) 10. Judgment by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. 11. Previous screening, enrollment or randomization in the present study. 12. For females only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding. 13. Participants without access to a smartphone or the internet.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Severe Asthma Exacerbation, While on Treatment Strategy, Interim Analysis Data Cut-off (Participants Aged >=12 Years) | From treatment initiation until the earliest occurrence of study completion, treatment discontinuation, step-up in maintenance therapy, or interim analysis DCO, up to one year following treatment initiation. | The time to first severe asthma exacerbation was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the length in days from treatment initiation until the date of the first severe asthma exacerbation event. Participants were censored at treatment discontinuation, a step-up in maintenance therapy, or interim analysis DCO. An asthma exacerbation was considered severe if it resulted in at least one of the following: use of systemic steroids for at least 3 days, inpatient hospitalization due to asthma or emergency room visit that required systemic steroids, or death due to asthma. The primary outcome measure was analyzed at the interim analysis (22 April 2024). Since the primary objective was met at the interim analysis, it was not re-tested at final database lock. Since fewer than 50% of participants had an exacerbation event, the median survival time could not be calculated and instead the number of participants with an event is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Severe Asthma Exacerbation, While on Treatment Strategy (Participants Aged >=18 Years) | From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation. | The time to first severe asthma exacerbation was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the length in days from treatment initiation until the date of first severe asthma exacerbation event, including all events that occurred up to the final DCO (20 September 2024). Participants were censored at treatment discontinuation or a step-up in maintenance therapy. An asthma exacerbation was considered severe if it results in at least one of the following: use of systemic steroids for at least 3 days, inpatient hospitalization due to asthma or emergency room visit that required systemic steroids, or death due to asthma. Since fewer than 50% of participants had an exacerbation event, the median survival time could not be calculated and instead the number of participants with an event is reported. |
| Time to First Severe Asthma Exacerbation, Treatment Policy Strategy (Participants Aged >=18 Years) | From treatment initiation until the earliest occurrence of study completion or withdrawal only, regardless of treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation. | The time to first severe asthma exacerbation was analyzed under the Treatment Policy strategy in the Full analysis set (FAS) and was defined as the length in days from treatment initiation until the date of first severe asthma exacerbation event, including all events that occurred up to the Final DCO (20 September 2024). Participants were censored at study completion or withdrawal. An asthma exacerbation was considered severe if it resulted in at least one of the following: use of systemic steroids for at least 3 days, inpatient hospitalization due to asthma or emergency room visit that required systemic steroids, or death due to asthma. Since fewer than 50% of participants had an exacerbation event, the median survival time could not be calculated and instead the number of participants with an event is reported. |
| Annualized Severe Asthma Exacerbation Rate, While on Treatment Strategy (Participants Aged >=12 Years) | From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation. | The annualized exacerbation rate was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the length in days from treatment initiation until the date of first severe asthma exacerbation event, including all events that occurred up to the final DCO (20 September 2024). Time at risk was defined as the cumulative number of days in the randomized treatment period across all participants in the treatment group, excluding the days during a severe exacerbation event and the 7 days following it resolving. An asthma exacerbation was considered severe if it resulted in at least one of the following: use of systemic steroids for at least 3 days, inpatient hospitalization due to asthma or emergency room visit that required systemic steroids, or death due to asthma. |
| Annualized Severe Asthma Exacerbation Rate, While on Treatment Strategy (Participants Aged >=18 Years) | From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation. | The annualized exacerbation rate was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the length in days from treatment initiation until the date of first severe asthma exacerbation event, including all events that occurred up to the final DCO (20 September 2024). Time at risk was defined as the cumulative number of days in the randomized treatment period across all participants in the treatment group, excluding the days during a severe exacerbation event and the 7 days following it resolving. An asthma exacerbation was considered severe if it resulted in at least one of the following: use of systemic steroids for at least 3 days, inpatient hospitalization due to asthma or emergency room visit that required systemic steroids, or death due to asthma. |
| Time to First Severe Asthma Exacerbation, Treatment Policy Strategy, Interim Analysis Data Cut-off (Participants Aged >=12 Years) | From treatment initiation until the earliest occurrence of study completion or withdrawal only, regardless of treatment discontinuation, a step-up in maintenance therapy or interim analysis DCO, up to one year following treatment initiation. | The time to first severe asthma exacerbation was analyzed under the Treatment Policy strategy in the Full analysis set (FAS) and was defined as the length in days from treatment initiation until the date of first severe asthma exacerbation occurred. Participants were censored at study completion or withdrawal, or the interim analysis DCO. An asthma exacerbation was considered severe if it resulted in at least one of the following: use of systemic steroids for at least 3 days, inpatient hospitalization due to asthma or emergency room visit that required systemic steroids, or death due to asthma. The key secondary outcome measure was analyzed at the interim analysis (22 April 2024). Since the key secondary objective was met at the interim analysis, it was not re-tested at final database lock. Since fewer than 50% of participants had an exacerbation event, the median survival time could not be calculated and instead the number of participants with an event is reported. |
| Total Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=18 Years) | From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation. | The total systemic glucocorticoid exposure was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the cumulative dose of SCS following a severe exacerbation from treatment initiation until study completion, treatment discontinuation or a step-up in maintenance therapy. SCS were normalized to prednisone equivalents when calculating total dose, patients whose total dose could not be normalized are excluded from analysis. |
| Total Duration of Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=12 Years) | From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation. | The total duration of systemic glucocorticoid exposure was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the cumulative days of SCS use following a severe exacerbation from treatment initiation until study completion, treatment discontinuation or a step-up in maintenance therapy. SCS were normalized to prednisone equivalents when calculating total dose, patients whose total dose could not be normalized are excluded from analysis. |
| Total Duration of Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=18 Years) | From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation. | The total duration of systemic glucocorticoid exposure was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the cumulative days of SCS use following a severe exacerbation from treatment initiation until study completion, treatment discontinuation or a step-up in maintenance therapy. SCS were normalized to prednisone equivalents when calculating total dose, patients whose total dose could not be normalized are excluded from analysis. |
| Total Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=12 Years) | From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation. | The total systemic glucocorticoid exposure was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the cumulative dose of SCS following a severe exacerbation from treatment initiation until study completion, treatment discontinuation or a step-up in maintenance therapy. SCS were normalized to prednisone equivalents when calculating total dose, patients whose total dose could not be normalized are excluded from analysis. |
Countries
United States
Participant flow
Recruitment details
The first participant was screened on 2 September 2022. Participants were enrolled at 54 sites in the United States. Primary and first secondary objectives were tested at the interim analysis, on data collected up to 22 April 2024. Following the decision to stop the study early for overwhelming efficacy, participants were instructed to attend their end of study visits. The last participant last visit occurred on 22 August 2024 and final database lock was achieved on 20 September 2024.
Pre-assignment details
A total of 5,221 participants were screened for this study, of which 2,516 participants were randomized to treatment; 2,705 were ineligible for participation in the trial. Of the 2,516 participants randomized, the full analysis set (ages 12 years and above) comprised of 2,421 participants as 95 participants discontinued the study prior to dosing randomized treatment.
Participants by arm
| Arm | Count |
|---|---|
| BDA MDI (PT027) 160/180 μg Budesonide/albuterol sulfate, BDA MDI, PT027
Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg: Budesonide/albuterol sulfate combination inhalation aerosol | 1,209 |
| AS MDI (PT007) 180 µg Albuterol sulfate MDI, PT007
Albuterol sulfate metered-dose inhaler 180 μg: Albuterol sulfate inhalation aerosol | 1,212 |
| Total | 2,421 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 20 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Lack of therapeutic response | 0 | 1 |
| Overall Study | Lost to Follow-up | 247 | 237 |
| Overall Study | Other | 17 | 13 |
| Overall Study | Physician Decision | 22 | 13 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Protocol Violation | 8 | 15 |
| Overall Study | Withdrawal by parent/guardian | 0 | 1 |
| Overall Study | Withdrawal by Subject | 51 | 64 |
Baseline characteristics
| Characteristic | BDA MDI (PT027) 160/180 μg | Total | AS MDI (PT007) 180 µg |
|---|---|---|---|
| Age, Categorical <=18 years | 29 Participants | 68 Participants | 39 Participants |
| Age, Categorical >=65 years | 80 Participants | 180 Participants | 100 Participants |
| Age, Categorical Between 18 and 65 years | 1100 Participants | 2173 Participants | 1073 Participants |
| Age, Continuous | 42.5 years STANDARD_DEVIATION 14.33 | 42.7 years STANDARD_DEVIATION 14.51 | 42.9 years STANDARD_DEVIATION 14.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 156 Participants | 292 Participants | 136 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1052 Participants | 2127 Participants | 1075 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 9 Participants | 14 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 28 Participants | 56 Participants | 28 Participants |
| Race/Ethnicity, Customized Black or African American | 219 Participants | 438 Participants | 219 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiple | 19 Participants | 43 Participants | 24 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 2 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Reported | 37 Participants | 69 Participants | 32 Participants |
| Race/Ethnicity, Customized Other | 47 Participants | 99 Participants | 52 Participants |
| Race/Ethnicity, Customized White | 848 Participants | 1697 Participants | 849 Participants |
| Sex: Female, Male Female | 810 Participants | 1653 Participants | 843 Participants |
| Sex: Female, Male Male | 399 Participants | 768 Participants | 369 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 1,257 | 1 / 1,259 |
| other Total, other adverse events | 227 / 1,209 | 232 / 1,212 |
| serious Total, serious adverse events | 37 / 1,209 | 37 / 1,212 |
Outcome results
Primary
Time to First Severe Asthma Exacerbation, While on Treatment Strategy, Interim Analysis Data Cut-off (Participants Aged >=12 Years)
The time to first severe asthma exacerbation was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the length in days from treatment initiation until the date of the first severe asthma exacerbation event. Participants were censored at treatment discontinuation, a step-up in maintenance therapy, or interim analysis DCO. An asthma exacerbation was considered severe if it resulted in at least one of the following: use of systemic steroids for at least 3 days, inpatient hospitalization due to asthma or emergency room visit that required systemic steroids, or death due to asthma. The primary outcome measure was analyzed at the interim analysis (22 April 2024). Since the primary objective was met at the interim analysis, it was not re-tested at final database lock. Since fewer than 50% of participants had an exacerbation event, the median survival time could not be calculated and instead the number of participants with an event is reported.
Time frame: From treatment initiation until the earliest occurrence of study completion, treatment discontinuation, step-up in maintenance therapy, or interim analysis DCO, up to one year following treatment initiation.
Population: Full analysis set; \>=12 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BDA MDI (PT027) 160/180 μg | Time to First Severe Asthma Exacerbation, While on Treatment Strategy, Interim Analysis Data Cut-off (Participants Aged >=12 Years) | 62 Participants |
| AS MDI (PT007) 180 µg | Time to First Severe Asthma Exacerbation, While on Treatment Strategy, Interim Analysis Data Cut-off (Participants Aged >=12 Years) | 110 Participants |
Comparison: Hazard ratios, 95% confidence intervals for hazard ratios and p-values are estimated using a Cox regression model with treatment group, pre-study asthma therapy, and number of severe exacerbations in the last 12 months prior to randomization as factors. A hazard ratio less than 1 favors the BDA MDI treatment group.p-value: <0.00195% CI: [0.392, 0.73]Regression, Cox
Secondary
Annualized Severe Asthma Exacerbation Rate, While on Treatment Strategy (Participants Aged >=12 Years)
The annualized exacerbation rate was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the length in days from treatment initiation until the date of first severe asthma exacerbation event, including all events that occurred up to the final DCO (20 September 2024). Time at risk was defined as the cumulative number of days in the randomized treatment period across all participants in the treatment group, excluding the days during a severe exacerbation event and the 7 days following it resolving. An asthma exacerbation was considered severe if it resulted in at least one of the following: use of systemic steroids for at least 3 days, inpatient hospitalization due to asthma or emergency room visit that required systemic steroids, or death due to asthma.
Time frame: From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation.
Population: Full analysis set; \>=12 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BDA MDI (PT027) 160/180 μg | Annualized Severe Asthma Exacerbation Rate, While on Treatment Strategy (Participants Aged >=12 Years) | 0.15 events per year |
| AS MDI (PT007) 180 µg | Annualized Severe Asthma Exacerbation Rate, While on Treatment Strategy (Participants Aged >=12 Years) | 0.32 events per year |
Comparison: Rates, rate ratios and two-sided p-values were estimated from a negative binomial model with treatment, pre-study asthma therapy, and number of severe exacerbations in the last 12 months prior to randomization as factors. A rate ratio less than 1 favors BDA MDI treatment group.p-value: <0.00195% CI: [0.34, 0.64]Negative binomial
Secondary
Annualized Severe Asthma Exacerbation Rate, While on Treatment Strategy (Participants Aged >=18 Years)
The annualized exacerbation rate was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the length in days from treatment initiation until the date of first severe asthma exacerbation event, including all events that occurred up to the final DCO (20 September 2024). Time at risk was defined as the cumulative number of days in the randomized treatment period across all participants in the treatment group, excluding the days during a severe exacerbation event and the 7 days following it resolving. An asthma exacerbation was considered severe if it resulted in at least one of the following: use of systemic steroids for at least 3 days, inpatient hospitalization due to asthma or emergency room visit that required systemic steroids, or death due to asthma.
Time frame: From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation.
Population: Full analysis set; \>=18 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BDA MDI (PT027) 160/180 μg | Annualized Severe Asthma Exacerbation Rate, While on Treatment Strategy (Participants Aged >=18 Years) | 0.15 events per year |
| AS MDI (PT007) 180 µg | Annualized Severe Asthma Exacerbation Rate, While on Treatment Strategy (Participants Aged >=18 Years) | 0.33 events per year |
Comparison: Rates, rate ratios and two-sided p-values were estimated from a negative binomial model with treatment, pre-study asthma therapy, and number of severe exacerbations in the last 12 months prior to randomization as factors. A rate ratio less than 1 favors BDA MDI treatment group.p-value: <0.00195% CI: [0.33, 0.63]Negative binomial
Secondary
Time to First Severe Asthma Exacerbation, Treatment Policy Strategy, Interim Analysis Data Cut-off (Participants Aged >=12 Years)
The time to first severe asthma exacerbation was analyzed under the Treatment Policy strategy in the Full analysis set (FAS) and was defined as the length in days from treatment initiation until the date of first severe asthma exacerbation occurred. Participants were censored at study completion or withdrawal, or the interim analysis DCO. An asthma exacerbation was considered severe if it resulted in at least one of the following: use of systemic steroids for at least 3 days, inpatient hospitalization due to asthma or emergency room visit that required systemic steroids, or death due to asthma. The key secondary outcome measure was analyzed at the interim analysis (22 April 2024). Since the key secondary objective was met at the interim analysis, it was not re-tested at final database lock. Since fewer than 50% of participants had an exacerbation event, the median survival time could not be calculated and instead the number of participants with an event is reported.
Time frame: From treatment initiation until the earliest occurrence of study completion or withdrawal only, regardless of treatment discontinuation, a step-up in maintenance therapy or interim analysis DCO, up to one year following treatment initiation.
Population: Full analysis set; \>=12 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BDA MDI (PT027) 160/180 μg | Time to First Severe Asthma Exacerbation, Treatment Policy Strategy, Interim Analysis Data Cut-off (Participants Aged >=12 Years) | 64 Participants |
| AS MDI (PT007) 180 µg | Time to First Severe Asthma Exacerbation, Treatment Policy Strategy, Interim Analysis Data Cut-off (Participants Aged >=12 Years) | 114 Participants |
Comparison: Hazard ratios, 95% confidence intervals for hazard ratios and p-values were estimated using a Cox regression model with treatment group, pre-study asthma therapy, and number of severe exacerbations in the last 12 months prior to randomization as factors. A hazard ratio less than 1 favors the BDA MDI treatment group.p-value: <0.00195% CI: [0.397, 0.733]Regression, Cox
Secondary
Time to First Severe Asthma Exacerbation, Treatment Policy Strategy (Participants Aged >=18 Years)
The time to first severe asthma exacerbation was analyzed under the Treatment Policy strategy in the Full analysis set (FAS) and was defined as the length in days from treatment initiation until the date of first severe asthma exacerbation event, including all events that occurred up to the Final DCO (20 September 2024). Participants were censored at study completion or withdrawal. An asthma exacerbation was considered severe if it resulted in at least one of the following: use of systemic steroids for at least 3 days, inpatient hospitalization due to asthma or emergency room visit that required systemic steroids, or death due to asthma. Since fewer than 50% of participants had an exacerbation event, the median survival time could not be calculated and instead the number of participants with an event is reported.
Time frame: From treatment initiation until the earliest occurrence of study completion or withdrawal only, regardless of treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation.
Population: Full analysis set; \>=18 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BDA MDI (PT027) 160/180 μg | Time to First Severe Asthma Exacerbation, Treatment Policy Strategy (Participants Aged >=18 Years) | 73 Participants |
| AS MDI (PT007) 180 µg | Time to First Severe Asthma Exacerbation, Treatment Policy Strategy (Participants Aged >=18 Years) | 131 Participants |
Comparison: Hazard ratios, 95% confidence intervals for hazard ratios and p-values were estimated using a Cox regression model with treatment group, pre-study asthma therapy, and number of severe exacerbations in the last 12 months prior to randomization as factors. A hazard ratio less than 1 favors the BDA MDI treatment group.p-value: <0.00195% CI: [0.406, 0.72]Regression, Cox
Secondary
Time to First Severe Asthma Exacerbation, While on Treatment Strategy (Participants Aged >=18 Years)
The time to first severe asthma exacerbation was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the length in days from treatment initiation until the date of first severe asthma exacerbation event, including all events that occurred up to the final DCO (20 September 2024). Participants were censored at treatment discontinuation or a step-up in maintenance therapy. An asthma exacerbation was considered severe if it results in at least one of the following: use of systemic steroids for at least 3 days, inpatient hospitalization due to asthma or emergency room visit that required systemic steroids, or death due to asthma. Since fewer than 50% of participants had an exacerbation event, the median survival time could not be calculated and instead the number of participants with an event is reported.
Time frame: From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation.
Population: Full analysis set; \>=18 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BDA MDI (PT027) 160/180 μg | Time to First Severe Asthma Exacerbation, While on Treatment Strategy (Participants Aged >=18 Years) | 71 Participants |
| AS MDI (PT007) 180 µg | Time to First Severe Asthma Exacerbation, While on Treatment Strategy (Participants Aged >=18 Years) | 126 Participants |
Comparison: Hazard ratios, 95% confidence intervals for hazard ratios and p-values were estimated using a Cox regression model with treatment group, pre-study asthma therapy, and number of severe exacerbations in the last 12 months prior to randomization as factors. A hazard ratio less than 1 favors the BDA MDI treatment group.p-value: <0.00195% CI: [0.405, 0.724]Regression, Cox
Secondary
Total Duration of Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=12 Years)
The total duration of systemic glucocorticoid exposure was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the cumulative days of SCS use following a severe exacerbation from treatment initiation until study completion, treatment discontinuation or a step-up in maintenance therapy. SCS were normalized to prednisone equivalents when calculating total dose, patients whose total dose could not be normalized are excluded from analysis.
Time frame: From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation.
Population: Full analysis set; \>=12 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BDA MDI (PT027) 160/180 μg | Total Duration of Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=12 Years) | 0.4 days | Standard Deviation 2.17 |
| AS MDI (PT007) 180 µg | Total Duration of Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=12 Years) | 0.9 days | Standard Deviation 3.66 |
Secondary
Total Duration of Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=18 Years)
The total duration of systemic glucocorticoid exposure was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the cumulative days of SCS use following a severe exacerbation from treatment initiation until study completion, treatment discontinuation or a step-up in maintenance therapy. SCS were normalized to prednisone equivalents when calculating total dose, patients whose total dose could not be normalized are excluded from analysis.
Time frame: From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation.
Population: Full analysis set; \>=18 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BDA MDI (PT027) 160/180 μg | Total Duration of Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=18 Years) | 0.4 days | Standard Deviation 2.2 |
| AS MDI (PT007) 180 µg | Total Duration of Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=18 Years) | 0.9 days | Standard Deviation 3.72 |
Secondary
Total Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=12 Years)
The total systemic glucocorticoid exposure was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the cumulative dose of SCS following a severe exacerbation from treatment initiation until study completion, treatment discontinuation or a step-up in maintenance therapy. SCS were normalized to prednisone equivalents when calculating total dose, patients whose total dose could not be normalized are excluded from analysis.
Time frame: From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation.
Population: Full analysis set; \>=12 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BDA MDI (PT027) 160/180 μg | Total Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=12 Years) | 23.2 mg/year |
| AS MDI (PT007) 180 µg | Total Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=12 Years) | 61.9 mg/year |
p-value: <0.001Wilcoxon rank sum
Secondary
Total Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=18 Years)
The total systemic glucocorticoid exposure was analyzed under the While on Treatment strategy in the Full analysis set (FAS) and was defined as the cumulative dose of SCS following a severe exacerbation from treatment initiation until study completion, treatment discontinuation or a step-up in maintenance therapy. SCS were normalized to prednisone equivalents when calculating total dose, patients whose total dose could not be normalized are excluded from analysis.
Time frame: From treatment initiation until the earliest occurrence of study completion, treatment discontinuation or a step-up in maintenance therapy, up to one year following treatment initiation.
Population: Full analysis set; \>=18 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BDA MDI (PT027) 160/180 μg | Total Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=18 Years) | 23.0 mg/year |
| AS MDI (PT007) 180 µg | Total Systemic Glucocorticoid Exposure, While on Treatment Strategy (Participants Aged >=18 Years) | 63.0 mg/year |
p-value: <0.001Wilcoxon rank sum