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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-003674-27 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BDA MDI (PT027) 160/180 μg | Experimental | Budesonide/Albuterol sulfate BDA MDI (PT027) high dose |
|
| BDA MDI (PT027) 80/180 μg | Experimental | Budesonide/Albuterol sulfate BDA MDI (PT027) low dose |
|
| BD MDI (PT008) 160 µg | Active Comparator | Budesonide BD MDI (PT008) |
|
| AS MDI (PT007) 180 µg | Active Comparator | Albuterol sulfate AS MDI (PT007) |
|
| Placebo MDI | Placebo Comparator | Placebo MDI |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 160/180 μg (high dose) | Combination Product | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Baseline and 12 weeks |
| 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. | Baseline and 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Female or male aged ≥4 years at the time of informed consent
Physician diagnosis of asthma with a documented history of the last 6 months
Receiving 1 of the following inhaled asthma medications with stable dosing for at least 30 days prior to Visit 1:
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.
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.
Demonstrate acceptable spirometry performance acceptability/repeatability criteria
Taken Ventolin on ≥2 days out of 7 days prior to Visit 2
Demonstrate acceptable metered dose inhaler (MDI) administration technique as assessed by the investigator.
Able to perform acceptable and reproducible peak expiratory flow measurements as assessed by the investigator
Exclusion Criteria:
Chronic obstructive pulmonary disease or other significant lung disease (eg, chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, or bronchopulmonary dysplasia)
Systemic corticosteroids (SCS) use (any dose and any indication) within 3 months before Visit 1
Chronic (≥3 weeks) use of SCS within 6 months prior to Visit 1
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
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)
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
Completed treatment for lower respiratory infection within 6 weeks prior to Visit 1
Upper respiratory infection involving antibiotic treatment not resolved within 7 days prior to Visit 1
Hospitalizations due to asthma within 6 months prior to Visit 1
Have taken ≥12 actuations per day of Sponsor-provided Ventolin during the run-in period prior to Visit 2 according to the below criteria:
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).
Historical or current evidence of a clinically significant disease
Cancer not in complete remission for at least 5 years before Visit 1
Hospitalization for psychiatric disorder or attempted suicide within 1 year of Visit 1
History of psychiatric disease, intellectual deficiency, poor motivation, or other conditions if their magnitude is limiting informed consent validity
Significant abuse of alcohol or drugs, in the opinion of the investigator
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| Name | Affiliation | Role |
|---|---|---|
| Frank Albers, MD, PhD | Avillion LLP | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Mobile | Alabama | 36608 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37003355 | Result | Chipps BE, Israel E, Beasley R, Panettieri RA Jr, Albers FC, Rees R, Dunsire L, Danilewicz A, Johnsson E, Cappelletti C, Papi A. Albuterol-Budesonide Pressurized Metered Dose Inhaler in Patients With Mild-to-Moderate Asthma: Results of the DENALI Double-Blind Randomized Controlled Trial. Chest. 2023 Sep;164(3):585-595. doi: 10.1016/j.chest.2023.03.035. Epub 2023 Mar 30. |
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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.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 6, 2020 | Jul 19, 2022 |
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| Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 80/180 μg (low dose) | Combination Product | 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) |
|
| Budesonide metered dose inhaler / BD MDI 160 µg | Drug | Budesonide pressurized metered dose inhaler (BD MDI) 160 micrograms (μg), given as 2 inhalations of BD MDI 80 μg, four times a day (QID) |
|
| Albuterol sulfate metered dose inhaler / AS MDI 180 μg | Drug | 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) |
|
| Placebo metered-dose inhaler / Placebo MDI | Other | Placebo pressurized metered dose inhaler (Placebo MDI), given as 2 inhalations of Placebo MDI, four times a day (QID) |
|
| From first dose (first inhalation of randomized treatment) up to about 40 minutes post-dose (Day 1). |
| 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. | 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). |
| 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. | Baseline and 12 weeks |
| 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. | Baseline and 1 week |
| Bakersfield |
| California |
| 93301 |
| United States |
| Research Site | Costa Mesa | California | 92627 | United States |
| Research Site | Encinitas | California | 92024 | United States |
| Research Site | Huntington Beach | California | 92647 | United States |
| Research Site | Lancaster | California | 93534 | United States |
| Research Site | Los Angeles | California | 90017 | United States |
| Research Site | Los Angeles | California | 90048 | United States |
| Research Site | Newport Beach | California | 92663 | United States |
| Research Site | Roseville | California | 95661 | United States |
| Research Site | Sacramento | California | 95823 | United States |
| Research Site | San Diego | California | 92123 | United States |
| Research Site | San Jose | California | 95117 | United States |
| Research Site | Waterbury | Connecticut | 06708 | United States |
| Research Site | Aventura | Florida | 33180 | United States |
| Research Site | Clearwater | Florida | 33765 | United States |
| Research Site | Gainesville | Florida | 32653 | United States |
| Research Site | Greenacres City | Florida | 33467 | United States |
| Research Site | Miami | Florida | 33126 | United States |
| Research Site | Miami | Florida | 33173 | United States |
| Research Site | Miami | Florida | 33174 | United States |
| Research Site | Miami | Florida | 33186 | United States |
| Research Site | Orlando | Florida | 32819 | United States |
| Research Site | Oviedo | Florida | 32765 | United States |
| Research Site | Palmetto Bay | Florida | 33157 | United States |
| Research Site | Pembroke Pines | Florida | 33024 | United States |
| Research Site | Pembroke Pines | Florida | 33026 | United States |
| Research Site | Meridian | Idaho | 83646 | United States |
| Research Site | Chicago | Illinois | 60602 | United States |
| Research Site | Chicago | Illinois | 60644 | United States |
| Research Site | White Marsh | Maryland | 21162 | United States |
| Research Site | Boston | Massachusetts | 02115 | United States |
| Research Site | North Dartmouth | Massachusetts | 02747 | United States |
| Research Site | Farmington Hills | Michigan | 48336 | United States |
| Research Site | Flint | Michigan | 48507 | United States |
| Research Site | Rochester Hills | Michigan | 48307 | United States |
| Research Site | Woodbury | Minnesota | 55125 | United States |
| Research Site | Columbia | Missouri | 65203 | United States |
| Research Site | Rolla | Missouri | 65401 | United States |
| Research Site | St Louis | Missouri | 63141 | United States |
| Research Site | Warrensburg | Missouri | 64093 | United States |
| Research Site | Missoula | Montana | 59808 | United States |
| Research Site | Bellevue | Nebraska | 68005 | United States |
| Research Site | Bellevue | Nebraska | 68123 | United States |
| Research Site | Las Vegas | Nevada | 89106 | United States |
| Research Site | Las Vegas | Nevada | 89119 | United States |
| Research Site | Skillman | New Jersey | 08558 | United States |
| Research Site | Toms River | New Jersey | 08755 | United States |
| Research Site | New Hyde Park | New York | 11040 | United States |
| Research Site | New York | New York | 10036 | United States |
| Research Site | The Bronx | New York | 10461 | United States |
| Research Site | Monroe | North Carolina | 28112 | United States |
| Research Site | Raleigh | North Carolina | 27607 | United States |
| Research Site | Oklahoma City | Oklahoma | 73106 | United States |
| Research Site | Oklahoma City | Oklahoma | 73112 | United States |
| Research Site | Tulsa | Oklahoma | 74136 | United States |
| Research Site | Medford | Oregon | 97504 | United States |
| Research Site | Portland | Oregon | 97202 | United States |
| Research Site | Erie | Pennsylvania | 16508 | United States |
| Research Site | Warwick | Rhode Island | 02886 | United States |
| Research Site | Gaffney | South Carolina | 29341 | United States |
| Research Site | Spartanburg | South Carolina | 29303 | United States |
| Research Site | Knoxville | Tennessee | 37909 | United States |
| Research Site | Austin | Texas | 78759 | United States |
| Research Site | Boerne | Texas | 78006 | United States |
| Research Site | Corsicana | Texas | 75110 | United States |
| Research Site | Dallas | Texas | 75225 | United States |
| Research Site | El Paso | Texas | 79903 | United States |
| Research Site | San Antonio | Texas | 78207 | United States |
| Research Site | San Antonio | Texas | 78229 | United States |
| Research Site | Sherman | Texas | 75092 | United States |
| Research Site | Morgantown | West Virginia | 26505 | United States |
| Research Site | Greenfield | Wisconsin | 53228 | United States |
| Research Site | Buenos Aires | 1128 | Argentina |
| Research Site | Buenos Aires | 1414 | Argentina |
| Research Site | Buenos Aires | 1425 | Argentina |
| Research Site | Buenos Aires | 1824 | Argentina |
| Research Site | Buenos Aires | 1878 | Argentina |
| Research Site | San Miguel de Tucumán | 4000 | Argentina |
| Research Site | Santa Fe | 2000 | Argentina |
| Research Site | Brandýs nad Labem | Czechia |
| Research Site | Kralupy nad Vltavou | Czechia |
| Research Site | Lovosice | Czechia |
| Research Site | Neratovice | Czechia |
| Research Site | Prague | Czechia |
| Research Site | Rokycany | Czechia |
| Research Site | Varnsdorf | Czechia |
| Research Site | Berlin | 10119 | Germany |
| Research Site | Berlin | 10787 | Germany |
| Research Site | Berlin | 12157 | Germany |
| Research Site | Berlin | 12159 | Germany |
| Research Site | Berlin | 12203 | Germany |
| Research Site | Berlin | 13187 | Germany |
| Research Site | Darmstadt | Germany |
| Research Site | Dortmund | Germany |
| Research Site | Frankfurt | Germany |
| Research Site | Halle | Germany |
| Research Site | Hamburg | Germany |
| Research Site | Hessen | Germany |
| Research Site | Leipzig | Germany |
| Research Site | Lübeck | Germany |
| Research Site | Marburg | Germany |
| Research Site | Munich | Germany |
| Research Site | Neu-Isenburg | Germany |
| Research Site | Sachsen | Germany |
| Research Site | Schleswig | Germany |
| Research Site | Wiesbaden | Germany |
| Research Site | Witten | Germany |
| Research Site | Belgrade | 11000 | Serbia |
| Research Site | Kamenitz | Serbia |
| Research Site | Kragujevac | Serbia |
| Research Site | Valjevo | Serbia |
| Research Site | Košice | Slovakia |
| Research Site | Žilina | Slovakia |
| Research Site | Cherkasy | Ukraine |
| Research Site | Dnipro | Ukraine |
| Research Site | Ivano-Frankivsk | Ukraine |
| Research Site | Kharkiv | 61002 | Ukraine |
| Research Site | Kharkiv | 61039 | Ukraine |
| Research Site | Kharkiv | 61124 | Ukraine |
| Research Site | Kherson | Ukraine |
| Research Site | Kyiv | 02002 | Ukraine |
| Research Site | Kyiv | 02232 | Ukraine |
| Research Site | Kyiv | 03680 | Ukraine |
| Research Site | Kyiv | 04201 | Ukraine |
| Research Site | Lutsk | Ukraine |
| Research Site | Vinnytsia | Ukraine |
| Research Site | Zaporizhzhya | 69035 | Ukraine |
| Research Site | Zaporizhzhya | 69600 | Ukraine |
| 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) |
| FG002 | 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) |
| FG003 | 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) |
| FG004 | 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) |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Of the 1,001 participants randomized, the full analysis set across all ages comprises 1,000 participants as one participant was randomized in error and did not receive study treatment. This participant has therefore been excluded from the summaries of baseline characteristics and efficacy.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| BG001 | 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) |
| BG002 | 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) |
| BG003 | 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) |
| BG004 | 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) |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Height | Mean | Standard Deviation | centimeters |
| |||||||||||||||
| Weight | Mean | Standard Deviation | kilograms |
| |||||||||||||||
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | Posted | Least Squares Mean | Standard Error | milliliters | Baseline and 12 weeks |
|
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| 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. | Posted | Least Squares Mean | Standard Error | milliliters | Baseline and 12 weeks |
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| 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. | 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. | Posted | Median | Full Range | minutes | From first dose (first inhalation of randomized treatment) up to about 40 minutes post-dose (Day 1). |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | Posted | Median | Full Range | Minutes | 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). |
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| 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. | 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. | Posted | Count of Participants | Participants | Baseline and 12 weeks |
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| 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. | Posted | Least Squares Mean | Standard Error | milliliters | Baseline and 1 week |
|
Approximately 12 weeks.
Adverse events were collected from the time of signed informed consent/assent and up to the safety follow up period. Reported adverse events are those that occurred from the date of first dose of randomized treatment up to the date of treatment discontinuation.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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) | 0 | 197 | 2 | 197 | 37 | 197 |
| EG001 | 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) | 0 | 204 | 4 | 204 | 31 | 204 |
| EG002 | 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) | 0 | 199 | 3 | 199 | 31 | 199 |
| EG003 | 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) | 0 | 201 | 1 | 201 | 29 | 201 |
| EG004 | 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) | 0 | 199 | 3 | 199 | 38 | 199 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Aortic dissection | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Foot deformity | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Metatarsalgia | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Influenza A virus test positive | Investigations | MedDRA (24.0) | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
Data or results obtained from this study must not be published without prior approval from the Sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Avillion LLP | +44 (0)203 764 9530 | avillion@avillionllp.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 28, 2021 | Jul 8, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D019819 | Budesonide |
| ID | Term |
|---|---|
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
Not provided
Not provided
| Adolescents (>=12 to <18 years) |
|
| Adults (>=18 to <65 years) |
|
| Elderly (>=65 years) |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| United States |
|
| Czechia |
|
| Ukraine |
|
| Slovakia |
|
| Serbia |
|
| Germany |
|
|
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. |
| ANCOVA |
| <0.001 |
| Mean Difference (Final Values) |
| 161.9 |
| 2-Sided |
| 95 |
| 109.4 |
| 214.5 |
| Superiority |
| 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. | ANCOVA | 0.003 | Mean Difference (Final Values) | 80.7 | 2-Sided | 95 | 28.4 | 132.9 | Superiority |
| OG003 | 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) |
| OG004 | 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) |
|
|
|
| OG002 | 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) |
| OG003 | 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) |
| OG004 | 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) |
|
|
|
| OG002 | 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) |
| OG003 | 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) |
| OG004 | 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) |
|
|
| OG002 | 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) |
| OG003 | 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) |
| OG004 | 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) |
|
|
|
| OG003 | 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) |
| OG004 | 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) |
|
|
|