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This is a multicenter, randomized, double-blind, single-dose, placebo-controlled, 2-period, crossover study to evaluate the efficacy and safety of budesonide/albuterol metered-dose inhaler (BDA MDI/PT027) as compared with a placebo metered-dose inhaler (placebo MDI) on exercise-induced bronchoconstriction (EIB) in adult and adolescent subjects with asthma. Subjects will receive each study treatment on separate visits and undergo a treadmill exercise challenge test for up to 10 minutes so that the effect of study treatment on exercise-induced bronchoconstriction can be evaluated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A/B - Treatment with BDA MDI 160/180 followed by treatment with Placebo MDI | Experimental | Subjects randomized to receive a single dose of BDA MDI 160/180 in treatment period 1, and a single dose of Placebo MDI in treatment period 2. |
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| B/A - Treatment with Placebo MDI followed by treatment with BDA MDI 160/180 | Experimental | Subjects randomized to receive a single dose of Placebo MDI in treatment period 1, and a single dose of BDA MDI 160/180 in treatment period 2. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg | Combination Product | Budesonide/albuterol sulfate combination inhalation aerosol single dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Percentage Fall From Post-dose, Pre-exercise Baseline in Forced Expiratory Volume in 1 Second (FEV₁) Observed up to 60 Minutes Post-exercise Challenge | Lung function was measured by spirometry. Spirometry assessments were completed 5 minutes before dosing, 30 minutes after dosing (baseline; 5 minutes before the exercise challenge), and then 5, 10, 15, 30, and 60 minutes after the exercise challenge. A reduction in FEV₁ was expected due to the effects of asthma and exercise on breathing and lung function. The percentage fall in FEV₁ was calculated based on the baseline value and maximum percentage fall value during the 60-minute assessment period. | Up to 60 minutes post exercise challenge |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects With a Maximum Percentage Fall in FEV₁ Post-exercise Challenge of <10% | The percentage fall in FEV₁ was calculated based on the baseline value and maximum percentage fall value during the 60-minute assessment period, and the percentage of subjects with a maximum percentage fall <10% was determined. | Up to 60 minutes post exercise challenge |
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Inclusion Criteria:
Female or male aged 12 to 70 years at the time of informed consent
Documented history of asthma for at least 6 months prior to Visit 1
Receiving 1 of the following asthma therapies with stable dosing for at least the 4 weeks before Visit 1; no other asthma therapies are permitted during the study:
Demonstrate acceptable MDI administration technique (use of a spacer device during the treatment phase is not permitted)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Frank Albers, MD, PhD | Avillion LLP | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Denver | Colorado | 80230 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34699967 | Result | LaForce C, Chipps BE, Albers FC, Reilly L, Johnsson E, Andrews H, Cappelletti C, Maes A, Papi A. Albuterol/budesonide for the treatment of exercise-induced bronchoconstriction in patients with asthma: The TYREE study. Ann Allergy Asthma Immunol. 2022 Feb;128(2):169-177. doi: 10.1016/j.anai.2021.10.020. Epub 2021 Oct 24. |
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The randomized treatment phase started after a 1 to 2 week screening period (Visits 1 and 2). In addition to the 60 subjects randomized, 71 subjects were screened but did not participate (70 screen failures, 1 withdrawal by subject).
Subjects included in the study were male and female adults and adolescents 12 to 70 years of age with a diagnosis of asthma as defined by the Global Initiative for Asthma (GINA) criteria and EIB as defined by a >=20% decrease from pre-exercise challenge best FEV₁ observed within 60 minutes after an exercise challenge at both screening visits. The first subject enrolled on 15 January 2020 and the last subject completed the study on 28 August 2020. Subjects were enrolled at 6 US study centers.
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| ID | Title | Description |
|---|---|---|
| FG000 | A/B - Treatment With BDA MDI 160/180 Followed by Treatment With Placebo MDI | Subjects randomized to receive a single dose of BDA MDI (PT027) at Visit 3/Period 1, and a single dose of placebo MDI at Visit 4/Period 2. Visit 3/Period 1 (Day 1) - Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg: Budesonide/albuterol sulfate combination inhalation aerosol single dose. Visit 4/Period 2 (Day 8 +/- 6 days) - Placebo metered-dose inhaler: Placebo inhalation aerosol single dose. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 (First Treatment Intervention) |
|
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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 | Oct 25, 2019 | Nov 1, 2021 |
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| Placebo metered-dose inhaler | Combination Product | Placebo inhalation aerosol single dose |
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| North Dartmouth |
| Massachusetts |
| 02747 |
| United States |
| Research Site | St Louis | Missouri | 63109 | United States |
| Research Site | Skillman | New Jersey | 08558 | United States |
| Research Site | Raleigh | North Carolina | 27607 | United States |
| Research Site | Burke | Virginia | 22015 | United States |
| FG001 | B/A - Treatment With Placebo MDI Followed by Treatment With BDA MDI 160/180 | Subjects randomized to receive a single dose of placebo MDI at Visit 3/Period 1, and a single dose of BDA MDI (PT027) at Visit 4/Period 2. Visit 3/Period 1 (Day 1) - Placebo metered-dose inhaler: Placebo inhalation aerosol single dose. Visit 4/Period 2 (Day 8 +/- 6 days) - Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg: Budesonide/albuterol sulfate combination inhalation aerosol single dose. |
| COMPLETED |
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| NOT COMPLETED |
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| Period 2 (Second Treatment Intervention) |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | A/B - Treatment With BDA MDI 160/180 Followed by Treatment With Placebo MDI | Subjects randomized to receive single dose of BDA MDI (PT027) at Visit 3/Period 1, and a single dose of placebo MDI at Visit 4/Period 2. Visit 3/Period 1 (Day 1) - Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg: Budesonide/albuterol sulfate combination inhalation aerosol single dose Visit 4/Period 2 (Day 8 +/- 6 days) - Placebo metered-dose inhaler: Placebo inhalation aerosol single dose |
| BG001 | B/A - Treatment With Placebo MDI Followed by Treatment With BDA MDI 160/180 | Subjects randomized to receive single dose of placebo MDI at Visit 3/Period 1, and a single dose of BDA MDI (PT027) at Visit 4/Period 2. Visit 3/Period 1 (Day 1) - Placebo metered-dose inhaler: Placebo inhalation aerosol single dose Visit 4/Period 2 (Day 8 +/- 6 days) - Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg: Budesonide/albuterol sulfate combination inhalation aerosol single dose |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Height | Mean | Standard Deviation | Centimeters |
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| Weight | Mean | Standard Deviation | Kilograms |
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| Body Mass Index | Mean | Standard Deviation | Kilograms per meter squared |
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| Maximal Heart Rate at Screening Visit 1 | Mean | Standard Deviation | Beats per minute |
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| Maximal Heart Rate at Screening Visit 2 | Mean | Standard Deviation | Beats per minute |
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| Pre-dose pre-ECT FEV₁ | Mean | Standard Deviation | Liters |
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| Pre-dose pre-ECT FEV₁ % predicted normal | Mean | Standard Deviation | Percentage of predicted normal |
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| Pre-dose pre-ECT FVC | Mean | Standard Deviation | Liters |
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| Pre-dose pre-ECT FEV₁/FVC | Mean | Standard Deviation | Percent |
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| Time since diagnosis of asthma to randomization | Median | Full Range | years |
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| 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 | Maximum Percentage Fall From Post-dose, Pre-exercise Baseline in Forced Expiratory Volume in 1 Second (FEV₁) Observed up to 60 Minutes Post-exercise Challenge | Lung function was measured by spirometry. Spirometry assessments were completed 5 minutes before dosing, 30 minutes after dosing (baseline; 5 minutes before the exercise challenge), and then 5, 10, 15, 30, and 60 minutes after the exercise challenge. A reduction in FEV₁ was expected due to the effects of asthma and exercise on breathing and lung function. The percentage fall in FEV₁ was calculated based on the baseline value and maximum percentage fall value during the 60-minute assessment period. | Posted | Least Squares Mean | 95% Confidence Interval | Maximum percentage fall FEV₁ | Up to 60 minutes post exercise challenge |
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| Secondary | Percentage of Subjects With a Maximum Percentage Fall in FEV₁ Post-exercise Challenge of <10% | The percentage fall in FEV₁ was calculated based on the baseline value and maximum percentage fall value during the 60-minute assessment period, and the percentage of subjects with a maximum percentage fall <10% was determined. | Posted | Count of Participants | Participants | Up to 60 minutes post exercise challenge |
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Approximately one week for each treatment intervention.
Safety population included all subjects who received at least one treatment intervention.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Intervention - BDA MDI 160/180 - All Subjects | Safety analysis of subjects receiving Treatment A - BDA MDI 160/180 | 0 | 60 | 0 | 60 | 0 | 60 |
| EG001 | Treatment Intervention - Placebo MDI - All Subjects | Safety analysis of subjects receiving Treatment B - Placebo MDI | 0 | 59 | 0 | 59 | 2 | 59 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anxiety | Psychiatric disorders | MedDRA (22.10) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (22.10) | Systematic Assessment |
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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 | Aug 7, 2020 | Nov 1, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D001250 | Asthma, Exercise-Induced |
| ID | Term |
|---|---|
| D001249 | Asthma |
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D012130 | Respiratory Hypersensitivity |
| D000092202 | Exercise-Induced Allergies |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D019819 | Budesonide |
| ID | Term |
|---|---|
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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