Asthma
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, multicenter, parallel group study to compare 2 dose levels of budesonide/albuterol BDA MDI (PT027) to its components budesonide BD MDI (PT008) and albuterol AS MDI (PT007) on improvement in lung function and asthma symptoms after 12 weeks of treatment in adult, adolescent, and child subjects with symptomatic asthma currently being treated with a short/rapid-acting β2-adrenoreceptor agonist (SABA) as needed alone or with low-dose inhaled corticosteroid (ICS) maintenance therapy plus SABA as needed.
Interventions
COMBINATION_PRODUCTBudesonide/albuterol sulfate metered dose inhaler / BDA MDI 160/180 μg (high dose)
Budesonide/albuterol sulfate pressurized metered dose inhaler (BDA MDI) 160/180 micrograms (μg), given as 2 inhalations of BDA MDI 80/90 μg, four times a day (QID)
COMBINATION_PRODUCTBudesonide/albuterol sulfate metered dose inhaler / BDA MDI 80/180 μg (low dose)
Budesonide/albuterol sulfate pressurized metered dose inhaler (BDA MDI) 80/180 micrograms (μg), given as 2 inhalations of BDA MDI 40/90 μg, four times a day (QID)
DRUGBudesonide metered dose inhaler / BD MDI 160 µg
Budesonide pressurized metered dose inhaler (BD MDI) 160 micrograms (μg), given as 2 inhalations of BD MDI 80 μg, four times a day (QID)
DRUGAlbuterol sulfate metered dose inhaler / AS MDI 180 μg
Albuterol sulfate pressurized metered dose inhaler (AS MDI) 180 micrograms (μg), given as 2 inhalations of AS MDI 90 μg, four times a day (QID)
OTHERPlacebo metered-dose inhaler / Placebo MDI
Placebo pressurized metered dose inhaler (Placebo MDI), given as 2 inhalations of Placebo MDI, four times a day (QID)
Sponsors
Bond Avillion 2 Development LP
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female or male aged ≥4 years at the time of informed consent 2. Physician diagnosis of asthma with a documented history of the last 6 months 3. Receiving 1 of the following inhaled asthma medications with stable dosing for at least 30 days prior to Visit 1: * Only short/rapid-acting β2-adrenoreceptor agonist (SABA) used as needed * Stable low-dose inhaled corticosteroid in addition to as-needed use of SABA 4. Pre-bronchodilator FEV1 of ≥50 to \<85% predicted normal value for adults (≥18 years of age) and ≥50% predicted normal value for subjects aged 4 to 17 years after withholding SABA ≥6 hours at Visit 1. 5. Demonstrate reversibility of airflow limitation defined as a ≥15% increase in FEV1 relative to baseline after administration of Sponsor-provided SABA (Ventolin) at either Visit 1 or Visit 1a. 6. Demonstrate acceptable spirometry performance acceptability/repeatability criteria 7. Taken Ventolin on ≥2 days out of 7 days prior to Visit 2 8. Demonstrate acceptable metered dose inhaler (MDI) administration technique as assessed by the investigator. 9. Able to perform acceptable and reproducible peak expiratory flow measurements as assessed by the investigator
Exclusion criteria
1. Chronic obstructive pulmonary disease or other significant lung disease (eg, chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, or bronchopulmonary dysplasia) 2. Systemic corticosteroids (SCS) use (any dose and any indication) within 3 months before Visit 1 3. Chronic (≥3 weeks) use of SCS within 6 months prior to Visit 1 4. Received any marketed (eg, omalizumab, mepolizumab, reslizumab, benralizumab) or investigational biologic within 3 months or 5 half-lives before Visit 1, whichever is longer, or any other prohibited medication 5. Current smokers, former smokers with \>10 pack-years history, or former smokers who stopped smoking \<6 months before Visit 1 (including all forms of tobacco, e-cigarettes \[vaping\], and marijuana) 6. Life-threatening asthma defined as any history of significant asthma episode(s) requiring admission to an intensive care unit, intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s) within 5 years of Visit 1 7. Completed treatment for lower respiratory infection within 6 weeks prior to Visit 1 8. Upper respiratory infection involving antibiotic treatment not resolved within 7 days prior to Visit 1 9. Hospitalizations due to asthma within 6 months prior to Visit 1 10. Have taken ≥12 actuations per day of Sponsor-provided Ventolin during the run-in period prior to Visit 2 according to the below criteria: * ≥2 days out of 14 days of run-in * ≥3 days out of 15 to 21 days of run-in * ≥4 days out of 22 or more days of run-in 11. Unable to comply with study procedures including non-compliance with diary completion (ie, \<70% subject completion of diary assessments in the last 7 days preceding Visit 2 or 4-times daily dosing, \<80% compliance during the placebo run-in period). 12. Historical or current evidence of a clinically significant disease 13. Cancer not in complete remission for at least 5 years before Visit 1 14. Hospitalization for psychiatric disorder or attempted suicide within 1 year of Visit 1 15. History of psychiatric disease, intellectual deficiency, poor motivation, or other conditions if their magnitude is limiting informed consent validity 16. Significant abuse of alcohol or drugs, in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Concentration Curve From 0 to 6 Hours (AUC0-6 Hours) Over 12 Weeks | Baseline and 12 weeks | Lung function will be measured by spirometry. Baseline FEV1 will be taken as the average of the 60- and 30-minute pre-dose spirometry measures on or before randomization. Starting with the first study drug dose at Week 0 and then at Week 12, spirometry assessments will be completed at 60 and 30 minutes before the morning dose and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes after dosing. FEV1 AUC0-6 hours will be calculated for changes from baseline (randomization visit) using the trapezoidal rule and will be normalized by dividing by the time (in hours) from dosing to the last measurement included (typically 6 hours). |
| Change From Baseline in Trough FEV1 | Baseline and 12 weeks | Trough FEV1 is calculated at each clinic visit as the average of the 30- and 60-minute pre-dose FEV1 measurements. Baseline FEV1 is defined as the average of the 30- and 60-minute pre-dose measures collected on the day of randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to 15% Increase in FEV1 Over the Pre-treatment Value on Day 1 | From first dose (first inhalation of randomized treatment) up to about 40 minutes post-dose (Day 1). | The time to onset is defined as the time (minutes) from the first inhalation of randomized treatment (Day 1) to the first instance where a percentage change from baseline in FEV1 of at least 15% is observed. Participants were only to be included in the analysis if a percent change from baseline of at least 15% is observed within a nominal 30 minutes post dose assessment time point. Baseline FEV1 is defined as the average of the 30- and 60- minute pre-dose spirometry measures taken at randomization. |
| Duration of 15% Increase in FEV1 Over the Pre-treatment Value on Day 1 | Onset up to about 40 minutes post-treatment, with duration lasting up to the last assessment of a nominal 6 hour serial spirometry profile (Day 1). | The duration of onset is defined as the time (minutes) of the continual period in which a percentage increase change from baseline in FEV1 of at least 15% is observed. Participants will only be included in the analyses if a percent change from baseline of at least 15% is observed within a nominal 30 minutes post dose assessment. If a participant has multiple periods of onset, only the first will contribute to the summary. Duration of onset can last up to the last assessment during a nominal 6 hour serial spirometry profile. Baseline FEV1 is defined as the average of the 60- and 30- minute pre-dose spirometry taken at randomization. |
| Number of Participants With a Clinically Meaningful Difference on the Asthma Control Questionnaire 7-item Version (ACQ-7) at Week 12. | Baseline and 12 weeks | A responder is defined as a participant who achieves a reduction from baseline in overall ACQ-7 score of at least 0.5. The ACQ-7 has 7 questions, with each question using a 7 point scale, where 0 = totally controlled and 6 = extremely poorly controlled. The overall ACQ-7 score is defined as the averaged score across the 7 questions. The analysis only includes participants who are uncontrolled at basellne, i.e. baseline ACQ-7 \>= 1.5. All participants who discontinue treatment prior to Week 12 are classified as non-responders. |
| Change From Baseline in Trough FEV1 at Week 1. | Baseline and 1 week | Trough FEV1 is calculated at each clinic visit as the average of the 60- and 30-minute pre-dose FEV1 measurements. Baseline FEV1 is defined as the average of the 60- and 30-minute pre-dose measures collected on the day of randomization. |
Countries
Argentina, Czechia, Germany, Serbia, Slovakia, Ukraine, United States
Participant flow
Recruitment details
The first subject enrolled on 20 March 2019 and the last subjected completed the study on 20 July 2021. Subjects were enrolled at 126 study centers worldwide (Argentina, Czechia, Germany, Serbia, Slovakia, Ukraine and the United States).
Pre-assignment details
The randomized treatment phase started after a 2 to 4 week screening period during which participants self-administered single-blind Placebo MDI QID and Ventolin as needed to be used in response to asthma symptoms. In addition to the 1,001 subjects randomized, 875 subjects were screened but did not participate, of which 851 (97.3%) were ineligible, 3 were lost to follow up, 1 was excluded due to a protocol deviation, 18 withdrew by subject decision, and 2 withdrew by parent/guardian decision.
Participants by arm
| Arm | Count |
|---|---|
| BDA MDI (PT027) 160/180 μg Budesonide/Albuterol sulfate BDA MDI (PT027) high dose
Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 160/180 μg (high dose): Budesonide/albuterol sulfate pressurized metered dose inhaler (BDA MDI) 160/180 micrograms (μg), given as 2 inhalations of BDA MDI 80/90 μg, four times a day (QID) | 197 |
| BDA MDI (PT027) 80/180 μg Budesonide/Albuterol sulfate BDA MDI (PT027) low dose
Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 80/180 μg (low dose): Budesonide/albuterol sulfate pressurized metered dose inhaler (BDA MDI) 80/180 micrograms (μg), given as 2 inhalations of BDA MDI 40/90 μg, four times a day (QID) | 204 |
| BD MDI (PT008) 160 µg Budesonide BD MDI (PT008)
Budesonide metered dose inhaler / BD MDI 160 µg: Budesonide pressurized metered dose inhaler (BD MDI) 160 micrograms (μg), given as 2 inhalations of BD MDI 80 μg, four times a day (QID) | 199 |
| AS MDI (PT007) 180 µg Albuterol sulfate AS MDI (PT007)
Albuterol sulfate metered dose inhaler / AS MDI 180 μg: Albuterol sulfate pressurized metered dose inhaler (AS MDI) 180 micrograms (μg), given as 2 inhalations of AS MDI 90 μg, four times a day (QID) | 201 |
| Placebo MDI Placebo MDI
Placebo metered-dose inhaler / Placebo MDI: Placebo pressurized metered dose inhaler (Placebo MDI), given as 2 inhalations of Placebo MDI, four times a day (QID) | 199 |
| Total | 1,000 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 3 | 2 | 4 |
| Overall Study | A severe exacerbation event | 0 | 0 | 0 | 0 | 3 |
| Overall Study | Condition under investigation worsened | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 2 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other reasons | 3 | 3 | 1 | 2 | 1 |
| Overall Study | Protocol Violation | 0 | 2 | 1 | 0 | 2 |
| Overall Study | Randomized in error and did not receive randomized study treatment | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by parent/guardian | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 10 | 5 | 9 | 8 |
Baseline characteristics
| Characteristic | BDA MDI (PT027) 160/180 μg | BDA MDI (PT027) 80/180 μg | BD MDI (PT008) 160 µg | AS MDI (PT007) 180 µg | Placebo MDI | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 50.0 years STANDARD_DEVIATION 15.8 | 48.7 years STANDARD_DEVIATION 16.79 | 48.3 years STANDARD_DEVIATION 15.8 | 47.0 years STANDARD_DEVIATION 16.79 | 48.6 years STANDARD_DEVIATION 15.82 | 48.5 years STANDARD_DEVIATION 16.21 |
| Age, Customized Adolescents (>=12 to <18 years) | 4 Participants | 7 Participants | 5 Participants | 5 Participants | 4 Participants | 25 Participants |
| Age, Customized Adults (>=18 to <65 years) | 154 Participants | 155 Participants | 161 Participants | 159 Participants | 161 Participants | 790 Participants |
| Age, Customized Children (>=4 to <12 years) | 0 Participants | 3 Participants | 0 Participants | 4 Participants | 3 Participants | 10 Participants |
| Age, Customized Elderly (>=65 years) | 39 Participants | 39 Participants | 33 Participants | 33 Participants | 31 Participants | 175 Participants |
| Body Mass Index | 28.537 kg/m^2 STANDARD_DEVIATION 5.2488 | 28.635 kg/m^2 STANDARD_DEVIATION 4.8491 | 28.477 kg/m^2 STANDARD_DEVIATION 4.914 | 29.016 kg/m^2 STANDARD_DEVIATION 4.8513 | 28.793 kg/m^2 STANDARD_DEVIATION 5.2534 | 28.691 kg/m^2 STANDARD_DEVIATION 5.0211 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 61 Participants | 62 Participants | 50 Participants | 46 Participants | 63 Participants | 282 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 136 Participants | 142 Participants | 149 Participants | 155 Participants | 136 Participants | 718 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 167.8 centimeters STANDARD_DEVIATION 8.61 | 166.8 centimeters STANDARD_DEVIATION 9.71 | 167.7 centimeters STANDARD_DEVIATION 9.92 | 168.6 centimeters STANDARD_DEVIATION 9.86 | 168.0 centimeters STANDARD_DEVIATION 10.85 | 167.8 centimeters STANDARD_DEVIATION 9.81 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 15 Participants | 18 Participants | 30 Participants | 19 Participants | 96 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 1 Participants | 3 Participants | 4 Participants | 14 Participants |
| Race (NIH/OMB) White | 179 Participants | 185 Participants | 180 Participants | 167 Participants | 174 Participants | 885 Participants |
| Region of Enrollment Argentina | 9 participants | 11 participants | 14 participants | 14 participants | 6 participants | 54 participants |
| Region of Enrollment Czechia | 12 participants | 12 participants | 12 participants | 17 participants | 18 participants | 71 participants |
| Region of Enrollment Germany | 28 participants | 30 participants | 27 participants | 29 participants | 24 participants | 138 participants |
| Region of Enrollment Serbia | 3 participants | 1 participants | 3 participants | 2 participants | 2 participants | 11 participants |
| Region of Enrollment Slovakia | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Ukraine | 44 participants | 44 participants | 43 participants | 32 participants | 40 participants | 203 participants |
| Region of Enrollment United States | 100 participants | 106 participants | 100 participants | 107 participants | 109 participants | 522 participants |
| Sex: Female, Male Female | 125 Participants | 128 Participants | 120 Participants | 121 Participants | 127 Participants | 621 Participants |
| Sex: Female, Male Male | 72 Participants | 76 Participants | 79 Participants | 80 Participants | 72 Participants | 379 Participants |
| Weight | 80.4 kilograms STANDARD_DEVIATION 16.43 | 80.0 kilograms STANDARD_DEVIATION 16.06 | 80.0 kilograms STANDARD_DEVIATION 14.52 | 82.3 kilograms STANDARD_DEVIATION 15.09 | 81.6 kilograms STANDARD_DEVIATION 17.79 | 80.9 kilograms STANDARD_DEVIATION 16.02 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 197 | 0 / 204 | 0 / 199 | 0 / 201 | 0 / 199 |
| other Total, other adverse events | 37 / 197 | 31 / 204 | 31 / 199 | 29 / 201 | 38 / 199 |
| serious Total, serious adverse events | 2 / 197 | 4 / 204 | 3 / 199 | 1 / 201 | 3 / 199 |
Outcome results
Primary
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Concentration Curve From 0 to 6 Hours (AUC0-6 Hours) Over 12 Weeks
Lung function will be measured by spirometry. Baseline FEV1 will be taken as the average of the 60- and 30-minute pre-dose spirometry measures on or before randomization. Starting with the first study drug dose at Week 0 and then at Week 12, spirometry assessments will be completed at 60 and 30 minutes before the morning dose and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes after dosing. FEV1 AUC0-6 hours will be calculated for changes from baseline (randomization visit) using the trapezoidal rule and will be normalized by dividing by the time (in hours) from dosing to the last measurement included (typically 6 hours).
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDA MDI (PT027) 160/180 μg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Concentration Curve From 0 to 6 Hours (AUC0-6 Hours) Over 12 Weeks | 258.6 milliliters | Standard Error 18.87 |
| BDA MDI (PT027) 80/180 μg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Concentration Curve From 0 to 6 Hours (AUC0-6 Hours) Over 12 Weeks | 242.2 milliliters | Standard Error 18.8 |
| BD MDI (PT008) 160 µg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Concentration Curve From 0 to 6 Hours (AUC0-6 Hours) Over 12 Weeks | 178.0 milliliters | Standard Error 18.79 |
| AS MDI (PT007) 180 µg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Concentration Curve From 0 to 6 Hours (AUC0-6 Hours) Over 12 Weeks | 157.2 milliliters | Standard Error 19.08 |
| Placebo MDI | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Concentration Curve From 0 to 6 Hours (AUC0-6 Hours) Over 12 Weeks | 96.7 milliliters | Standard Error 19.02 |
Comparison: Only includes data from date of first dose up to date of last dose of randomized treatment. A sequential testing strategy is used such that the primary hypothesis tests are listed in ascending order of sequence. A null hypothesis can only be rejected if all preceding null hypotheses are also rejected. Tests are each conducted at the 5% level of significance.p-value: 0.02595% CI: [7.7, 113.4]ANCOVA
Comparison: Only includes data from date of first dose up to date of last dose of randomized treatment. A sequential testing strategy is used such that the primary hypothesis tests are listed in ascending order of sequence. A null hypothesis can only be rejected if all preceding null hypotheses are also rejected. Tests are each conducted at the 5% level of significance.p-value: <0.00195% CI: [109.4, 214.5]ANCOVA
Comparison: Only includes data from date of first dose up to date of last dose of randomized treatment. A sequential testing strategy is used such that the primary hypothesis tests are listed in ascending order of sequence. A null hypothesis can only be rejected if all preceding null hypotheses are also rejected. Tests are each conducted at the 5% level of significance.p-value: 0.00395% CI: [28.4, 132.9]ANCOVA
Primary
Change From Baseline in Trough FEV1
Trough FEV1 is calculated at each clinic visit as the average of the 30- and 60-minute pre-dose FEV1 measurements. Baseline FEV1 is defined as the average of the 30- and 60-minute pre-dose measures collected on the day of randomization.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDA MDI (PT027) 160/180 μg | Change From Baseline in Trough FEV1 | 135.5 milliliters | Standard Error 24.58 |
| BDA MDI (PT027) 80/180 μg | Change From Baseline in Trough FEV1 | 123.5 milliliters | Standard Error 24.65 |
| BD MDI (PT008) 160 µg | Change From Baseline in Trough FEV1 | 108.9 milliliters | Standard Error 24.51 |
| AS MDI (PT007) 180 µg | Change From Baseline in Trough FEV1 | 2.7 milliliters | Standard Error 25.24 |
| Placebo MDI | Change From Baseline in Trough FEV1 | 35.6 milliliters | Standard Error 25.12 |
Comparison: Only includes data from date of first dose up to date of last dose of randomized treatment. A sequential testing strategy is used such that the primary hypothesis tests are listed in ascending order of sequence. A null hypothesis can only be rejected if all preceding null hypotheses are also rejected. Tests are each conducted at the 5% level of significance.p-value: 0.03795% CI: [4.4, 142.2]ANCOVA
Comparison: Only includes data from date of first dose up to date of last dose of randomized treatment. A sequential testing strategy is used such that the primary hypothesis tests are listed in ascending order of sequence. A null hypothesis can only be rejected if all preceding null hypotheses are also rejected. Tests are each conducted at the 5% level of significance.p-value: 0.00595% CI: [30.9, 168.8]ANCOVA
Comparison: Only includes data from date of first dose up to date of last dose of randomized treatment. A sequential testing strategy is used such that the primary hypothesis tests are listed in ascending order of sequence. A null hypothesis can only be rejected if all preceding null hypotheses are also rejected. Tests are each conducted at the 5% level of significance.p-value: <0.00195% CI: [63.6, 201.9]ANCOVA
Comparison: Only includes data from date of first dose up to date of last dose of randomized treatment. A sequential testing strategy is used such that the primary hypothesis tests are listed in ascending order of sequence. A null hypothesis can only be rejected if all preceding null hypotheses are also rejected. Tests are each conducted at the 5% level of significance.p-value: 0.01395% CI: [18.8, 156.9]ANCOVA
Comparison: Only includes data from date of first dose up to date of last dose of randomized treatment. A sequential testing strategy is used such that the primary hypothesis tests are listed in ascending order of sequence. A null hypothesis can only be rejected if all preceding null hypotheses are also rejected. Tests are each conducted at the 5% level of significance.p-value: <0.00195% CI: [51.5, 190.1]ANCOVA
Secondary
Change From Baseline in Trough FEV1 at Week 1.
Trough FEV1 is calculated at each clinic visit as the average of the 60- and 30-minute pre-dose FEV1 measurements. Baseline FEV1 is defined as the average of the 60- and 30-minute pre-dose measures collected on the day of randomization.
Time frame: Baseline and 1 week
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BDA MDI (PT027) 160/180 μg | Change From Baseline in Trough FEV1 at Week 1. | 107.2 milliliters | Standard Error 21.46 |
| BDA MDI (PT027) 80/180 μg | Change From Baseline in Trough FEV1 at Week 1. | 72.0 milliliters | Standard Error 21.31 |
| BD MDI (PT008) 160 µg | Change From Baseline in Trough FEV1 at Week 1. | 93.4 milliliters | Standard Error 21.35 |
| AS MDI (PT007) 180 µg | Change From Baseline in Trough FEV1 at Week 1. | -0.8 milliliters | Standard Error 21.69 |
| Placebo MDI | Change From Baseline in Trough FEV1 at Week 1. | 41.3 milliliters | Standard Error 21.47 |
Comparison: Comparison is not type-I error controlled.p-value: 0.16995% CI: [-101.9, 17.8]ANCOVA
Comparison: Comparison is not type-I error controlled.p-value: 0.08695% CI: [-7.4, 111.5]ANCOVA
Comparison: Comparison is not type-I error controlled.p-value: 0.3195% CI: [-28.6, 90.1]ANCOVA
Comparison: Comparison is not type-I error controlled.p-value: 0.0395% CI: [6.3, 125.4]ANCOVA
Comparison: Comparison is not type-I error controlled.p-value: 0.01795% CI: [13.1, 132.5]ANCOVA
Comparison: Comparison is not type-I error controlled.p-value: <0.00195% CI: [48.1, 167.8]ANCOVA
Comparison: Comparison is not type-I error controlled.p-value: 0.4895% CI: [-80.5, 37.9]ANCOVA
Comparison: Comparison is not type-I error controlled.p-value: 0.64895% CI: [-45.6, 73.2]ANCOVA
Comparison: Comparison is not type-I error controlled.p-value: 0.24695% CI: [-24.2, 94.5]ANCOVA
Secondary
Duration of 15% Increase in FEV1 Over the Pre-treatment Value on Day 1
The duration of onset is defined as the time (minutes) of the continual period in which a percentage increase change from baseline in FEV1 of at least 15% is observed. Participants will only be included in the analyses if a percent change from baseline of at least 15% is observed within a nominal 30 minutes post dose assessment. If a participant has multiple periods of onset, only the first will contribute to the summary. Duration of onset can last up to the last assessment during a nominal 6 hour serial spirometry profile. Baseline FEV1 is defined as the average of the 60- and 30- minute pre-dose spirometry taken at randomization.
Time frame: Onset up to about 40 minutes post-treatment, with duration lasting up to the last assessment of a nominal 6 hour serial spirometry profile (Day 1).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BDA MDI (PT027) 160/180 μg | Duration of 15% Increase in FEV1 Over the Pre-treatment Value on Day 1 | 185.5 Minutes |
| BDA MDI (PT027) 80/180 μg | Duration of 15% Increase in FEV1 Over the Pre-treatment Value on Day 1 | 174 Minutes |
| BD MDI (PT008) 160 µg | Duration of 15% Increase in FEV1 Over the Pre-treatment Value on Day 1 | 98 Minutes |
| AS MDI (PT007) 180 µg | Duration of 15% Increase in FEV1 Over the Pre-treatment Value on Day 1 | 158.5 Minutes |
| Placebo MDI | Duration of 15% Increase in FEV1 Over the Pre-treatment Value on Day 1 | 229.5 Minutes |
Secondary
Number of Participants With a Clinically Meaningful Difference on the Asthma Control Questionnaire 7-item Version (ACQ-7) at Week 12.
A responder is defined as a participant who achieves a reduction from baseline in overall ACQ-7 score of at least 0.5. The ACQ-7 has 7 questions, with each question using a 7 point scale, where 0 = totally controlled and 6 = extremely poorly controlled. The overall ACQ-7 score is defined as the averaged score across the 7 questions. The analysis only includes participants who are uncontrolled at basellne, i.e. baseline ACQ-7 \>= 1.5. All participants who discontinue treatment prior to Week 12 are classified as non-responders.
Time frame: Baseline and 12 weeks
Population: The analysis only includes participants who are uncontrolled at baseline, i.e. ACQ-7 \>= 1.5. All participants who discontinue treatment prior to Week 12 are classified as non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BDA MDI (PT027) 160/180 μg | Number of Participants With a Clinically Meaningful Difference on the Asthma Control Questionnaire 7-item Version (ACQ-7) at Week 12. | 107 Participants |
| BDA MDI (PT027) 80/180 μg | Number of Participants With a Clinically Meaningful Difference on the Asthma Control Questionnaire 7-item Version (ACQ-7) at Week 12. | 108 Participants |
| BD MDI (PT008) 160 µg | Number of Participants With a Clinically Meaningful Difference on the Asthma Control Questionnaire 7-item Version (ACQ-7) at Week 12. | 100 Participants |
| AS MDI (PT007) 180 µg | Number of Participants With a Clinically Meaningful Difference on the Asthma Control Questionnaire 7-item Version (ACQ-7) at Week 12. | 77 Participants |
| Placebo MDI | Number of Participants With a Clinically Meaningful Difference on the Asthma Control Questionnaire 7-item Version (ACQ-7) at Week 12. | 88 Participants |
Comparison: Comparison is not type-I error controlled.p-value: 0.11895% CI: [0.445, 1.096]Regression, Logistic
Comparison: Comparison is not type-I error controlled.p-value: 0.16195% CI: [0.878, 2.187]Regression, Logistic
Comparison: Comparison is not type-I error controlled.p-value: 0.04495% CI: [1.013, 2.541]Regression, Logistic
Comparison: Comparison is not type-I error controlled.p-value: 0.03995% CI: [1.024, 2.584]Regression, Logistic
Comparison: Comparison is not type-I error controlled.p-value: <0.00195% CI: [1.456, 3.626]Regression, Logistic
Comparison: Comparison is not type-I error controlled.p-value: <0.00195% CI: [1.471, 3.687]Regression, Logistic
Comparison: Comparison is not type-I error controlled.p-value: 0.53295% CI: [0.731, 1.835]Regression, Logistic
Comparison: Comparison is not type-I error controlled.p-value: 0.49995% CI: [0.737, 1.868]Regression, Logistic
Comparison: Comparison is not type-I error controlled.p-value: 0.95595% CI: [0.635, 1.618]Regression, Logistic
Secondary
Time to 15% Increase in FEV1 Over the Pre-treatment Value on Day 1
The time to onset is defined as the time (minutes) from the first inhalation of randomized treatment (Day 1) to the first instance where a percentage change from baseline in FEV1 of at least 15% is observed. Participants were only to be included in the analysis if a percent change from baseline of at least 15% is observed within a nominal 30 minutes post dose assessment time point. Baseline FEV1 is defined as the average of the 30- and 60- minute pre-dose spirometry measures taken at randomization.
Time frame: From first dose (first inhalation of randomized treatment) up to about 40 minutes post-dose (Day 1).
Population: Participants were only included in the analyses if a percent change from baseline of at least 15% is observed within the nominal 30 minutes post-dose.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BDA MDI (PT027) 160/180 μg | Time to 15% Increase in FEV1 Over the Pre-treatment Value on Day 1 | 7.5 minutes |
| BDA MDI (PT027) 80/180 μg | Time to 15% Increase in FEV1 Over the Pre-treatment Value on Day 1 | 7.0 minutes |
| BD MDI (PT008) 160 µg | Time to 15% Increase in FEV1 Over the Pre-treatment Value on Day 1 | 17.0 minutes |
| AS MDI (PT007) 180 µg | Time to 15% Increase in FEV1 Over the Pre-treatment Value on Day 1 | 9.5 minutes |
| Placebo MDI | Time to 15% Increase in FEV1 Over the Pre-treatment Value on Day 1 | 14.0 minutes |
Comparison: Not type-I error controlled. The estimated median difference and 95% CIs are calculated using the Hodges-Lehmann method.95% CI: [-6, 1]
Comparison: Not type-I error controlled. The estimated median difference and 95% CIs are calculated using the Hodges-Lehmann method.95% CI: [-3, 9]
Comparison: Not type-I error controlled. The estimated median difference and 95% CIs are calculated using the Hodges-Lehmann method.95% CI: [-9, 0]
Comparison: Not type-I error controlled. The estimated median difference and 95% CIs are calculated using the Hodges-Lehmann method.95% CI: [-9, 0]
Comparison: Not type-I error controlled. The estimated median difference and 95% CIs are calculated using the Hodges-Lehmann method.95% CI: [-3, 0]
Comparison: Not type-I error controlled. The estimated median difference and 95% CIs are calculated using the Hodges-Lehmann method.95% CI: [-2, 0]
Comparison: Not type-I error controlled. The estimated median difference and 95% CIs are calculated using the Hodges-Lehmann method.95% CI: [-11, -2]
Comparison: Not type-I error controlled. The estimated median difference and 95% CIs are calculated using the Hodges-Lehmann method.95% CI: [-11, -2]
Comparison: Not type-I error controlled. The estimated median difference and 95% CIs are calculated using the Hodges-Lehmann method.95% CI: [-1, 1]