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TYREE: A Study to Assess the Efficacy of Budesonide/Albuterol Metered-dose Inhaler (BDA MDI/PT027) on Exercise-induced Bronchoconstriction in Adults and Adolescents With Asthma

Sponsor
Bond Avillion 2 Development LP (Industry)
Overall Status
Completed
CT.gov ID
NCT04234464
Collaborator
(none)
60
Enrollment
6
Locations
2
Arms
7.4
Actual Duration (Months)
10
Patients Per Site
1.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg
  • Combination Product: Placebo metered-dose inhaler
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Single-dose, 2-Period, Crossover Study to Assess the Efficacy of PT027 Compared With Placebo on Exercise-Induced Bronchoconstriction in Adult and Adolescent Subjects With Asthma
Actual Study Start Date :
Jan 15, 2020
Actual Primary Completion Date :
Aug 28, 2020
Actual Study Completion Date :
Aug 28, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: A/B - Treatment with BDA MDI 160/180 followed by treatment with Placebo MDI

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.

Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg
Budesonide/albuterol sulfate combination inhalation aerosol single dose
Other Names:
  • BDA MDI 160/180 μg (PT027)

    • Combination Product: Placebo metered-dose inhaler
    Placebo inhalation aerosol single dose
    Other Names:
  • Placebo MDI

    		•
    Experimental: B/A - Treatment with Placebo MDI followed by treatment with BDA MDI 160/180

    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.

    Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg
    Budesonide/albuterol sulfate combination inhalation aerosol single dose
    Other Names:
  • BDA MDI 160/180 μg (PT027)

    • Combination Product: Placebo metered-dose inhaler
    Placebo inhalation aerosol single dose
    Other Names:
  • Placebo MDI

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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 [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.

    Secondary Outcome Measures

    1. Percentage of Subjects With a Maximum Percentage Fall in FEV₁ Post-exercise Challenge of <10% [Up to 60 minutes post exercise challenge]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Female or male aged 12 to 70 years at the time of informed consent

    2. Documented history of asthma for at least 6 months prior to Visit 1

    3. 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:

    • Short/rapid-acting β 2-adrenoreceptor agonist (SABA) used as needed

    • Low- to medium-dose maintenance therapy with inhaled corticosteroid (ICS) and SABA used as needed

    1. Demonstrate acceptable MDI administration technique (use of a spacer device during the treatment phase is not permitted)
    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), including regular or occasional use of oxygen

    2. Systemic corticosteroids (SCS) use (any dose and any indication) within 3 months before Visit 1

    3. History of life-threatening asthma, defined by past intubations for asthma, or intensive care unit admission for asthma within the prior 24 months

    4. Receiving regular maintenance treatment with prohibited anti-inflammatory or long-acting bronchodilator asthma medication (inhaled, nebulized, oral, or systemic) within 1 month prior to Visit 1

    5. Unable to tolerate the lung function testing performed after exercise challenge test without use of rescue medication

    6. 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)

    7. Completed treatment for lower respiratory infection within 6 weeks prior to Visit 1, regardless if resulting in accompanying asthma symptoms aggravation or not

    8. Upper respiratory infection involving antibiotic treatment not resolved within 7 days prior to Visit 1

    9. Received any marketed (eg, omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab) or investigational biologic within 3 months before Visit 1, or any other prohibited medication

    10. Current treatment with any investigational product or within the last 30 days of Visit

    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 or intellectual deficiency

    16. Having a scheduled or planned hospitalization during the study

    17. Inability (and/or unwillingness) to abstain from protocol-defined prohibited medications during the study.

    18. Use of any herbal products by inhalation or nebulizer within 2 weeks of Visit 1 and/or the unwillingness to stop during the study duration.

    19. Significant abuse of alcohol or drugs

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Denver Colorado United States 80230
    2 Research Site North Dartmouth Massachusetts United States 02747
    3 Research Site Saint Louis Missouri United States 63109
    4 Research Site Skillman New Jersey United States 08558
    5 Research Site Raleigh North Carolina United States 27607
    6 Research Site Burke Virginia United States 22015

    Sponsors and Collaborators

    • Bond Avillion 2 Development LP

    Investigators

    • Study Director: Frank Albers, MD, PhD, Avillion LLP

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Bond Avillion 2 Development LP
    ClinicalTrials.gov Identifier:
    NCT04234464
    Other Study ID Numbers:
    • AV005
    First Posted:
    Jan 21, 2020
    Last Update Posted:
    Jan 13, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Bronchial Spasm
    Asthma, Exercise-Induced
    Budesonide
    Albuterol

    Study Results

    Participant Flow

    Recruitment Details 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.
    Pre-assignment Detail 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).
    Arm/Group Title A/B - Treatment With BDA MDI 160/180 Followed by Treatment With Placebo MDI B/A - Treatment With Placebo MDI Followed by Treatment With BDA MDI 160/180
    Arm/Group Description 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. 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.
    Period Title: Period 1 (First Treatment Intervention)
    STARTED 29 31
    COMPLETED 29 31
    NOT COMPLETED 0 0
    Period Title: Period 1 (First Treatment Intervention)
    STARTED 29 31
    COMPLETED 28 31
    NOT COMPLETED 1 0

    Baseline Characteristics

    Arm/Group Title A/B - Treatment With BDA MDI 160/180 Followed by Treatment With Placebo MDI B/A - Treatment With Placebo MDI Followed by Treatment With BDA MDI 160/180 Total
    Arm/Group Description 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 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 Total of all reporting groups
    Overall Participants 29 31 60
    Age (Count of Participants)
    <=18 years
    1
    3.4%
    1
    3.2%
    2
    3.3%
    Between 18 and 65 years
    27
    93.1%
    30
    96.8%
    57
    95%
    >=65 years
    1
    3.4%
    0
    0%
    1
    1.7%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    39.1
    (12.28)
    41.8
    (11.31)
    40.5
    (11.76)
    Sex: Female, Male (Count of Participants)
    Female
    21
    72.4%
    17
    54.8%
    38
    63.3%
    Male
    8
    27.6%
    14
    45.2%
    22
    36.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    3
    9.7%
    3
    5%
    Not Hispanic or Latino
    29
    100%
    28
    90.3%
    57
    95%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    2
    6.9%
    0
    0%
    2
    3.3%
    Native Hawaiian or Other Pacific Islander
    1
    3.4%
    0
    0%
    1
    1.7%
    Black or African American
    5
    17.2%
    13
    41.9%
    18
    30%
    White
    21
    72.4%
    18
    58.1%
    39
    65%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    29
    100%
    31
    100%
    60
    100%
    Height (Centimeters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Centimeters]
    167.0
    (9.41)
    170.7
    (10.28)
    168.9
    (9.96)
    Weight (Kilograms) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Kilograms]
    81.3
    (18.50)
    84.4
    (21.60)
    82.9
    (20.05)
    Body Mass Index (Kilograms per meter squared) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Kilograms per meter squared]
    29.0
    (5.51)
    28.7
    (5.52)
    28.8
    (5.47)
    Maximal Heart Rate at Screening Visit 1 (Beats per minute) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Beats per minute]
    167.2
    (15.11)
    164.1
    (12.71)
    165.6
    (13.90)
    Maximal Heart Rate at Screening Visit 2 (Beats per minute) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Beats per minute]
    166.3
    (15.83)
    163.3
    (12.88)
    164.8
    (14.34)
    Pre-dose pre-ECT FEV₁ (Liters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Liters]
    2.712
    (0.5895)
    2.608
    (0.6409)
    2.658
    (0.6137)
    Pre-dose pre-ECT FEV₁ % predicted normal (Percentage of predicted normal) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Percentage of predicted normal]
    84.86
    (12.914)
    78.24
    (6.567)
    81.44
    (10.593)
    Pre-dose pre-ECT FVC (Liters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Liters]
    3.823
    (0.9770)
    3.546
    (1.0576)
    3.680
    (1.0204)
    Pre-dose pre-ECT FEV₁/FVC (Percent) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Percent]
    71.88
    (8.143)
    74.97
    (9.051)
    73.47
    (8.692)
    Time since diagnosis of asthma to randomization (years) [Median (Full Range) ]
    Median (Full Range) [years]
    25.19
    28.59
    27.36

    Outcome Measures

    1. Primary Outcome
    Title 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
    Description 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.
    Time Frame Up to 60 minutes post exercise challenge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment Intervention A - BDA MDI 160/180 - All Subjects Treatment Intervention B - Placebo MDI - All Subjects
    Arm/Group Description Analysis of subjects receiving Treatment Intervention A - BDA MDI 160/180 Analysis of subjects receiving Treatment Intervention B - Placebo MDI
    Measure Participants 60 59
    Least Squares Mean (95% Confidence Interval) [Maximum percentage fall FEV₁]
    5.45
    18.97
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Treatment Intervention A - BDA MDI 160/180 - All Subjects, Treatment Intervention B - Placebo MDI - All Subjects
    Comments Maximum percentage fall in post-dose pre-exercise FEV₁ up to 60 minutes post-exercise challenge is analyzed using a mixed effects model adjusted for treatment, treatment period, treatment sequence as categorical fixed effects, period-specific pre-dose baseline FEV₁ and average pre-dose baseline FEV₁ as continuous covariates, and a random subject within treatment sequence effect.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 13.51
    Confidence Interval (2-Sided) 95%
    10.09 to 16.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Subjects With a Maximum Percentage Fall in FEV₁ Post-exercise Challenge of <10%
    Description 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.
    Time Frame Up to 60 minutes post exercise challenge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment Intervention A - BDA MDI 160/180 - All Subjects Treatment Intervention B - Placebo MDI - All Subjects
    Arm/Group Description Analysis of subjects receiving Treatment Intervention A - BDA MDI 160/180 Analysis of subjects receiving Treatment Intervention B - Placebo MDI
    Measure Participants 60 60
    Count of Participants [Participants]
    47
    162.1%
    17
    54.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Treatment Intervention A - BDA MDI 160/180 - All Subjects, Treatment Intervention B - Placebo MDI - All Subjects
    Comments A generalized linear mixed model with logit link adjusted for treatment, treatment period and treatment sequence as fixed effects, pre-dose baseline FEV₁ and average pre-dose baseline FEV₁ as continuous covariates, and a random subject within treatment sequence effect.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 10.548
    Confidence Interval (2-Sided) 95%
    4.311 to 25.805
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Approximately one week for each treatment intervention.
    Adverse Event Reporting Description Safety population included all subjects who received at least one treatment intervention.
    Arm/Group Title Treatment Intervention - BDA MDI 160/180 - All Subjects Treatment Intervention - Placebo MDI - All Subjects
    Arm/Group Description Safety analysis of subjects receiving Treatment A - BDA MDI 160/180 Safety analysis of subjects receiving Treatment B - Placebo MDI
    All Cause Mortality
    Treatment Intervention - BDA MDI 160/180 - All Subjects Treatment Intervention - Placebo MDI - All Subjects
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/60 (0%) 0/59 (0%)
    Serious Adverse Events
    Treatment Intervention - BDA MDI 160/180 - All Subjects Treatment Intervention - Placebo MDI - All Subjects
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/60 (0%) 0/59 (0%)
    Other (Not Including Serious) Adverse Events
    Treatment Intervention - BDA MDI 160/180 - All Subjects Treatment Intervention - Placebo MDI - All Subjects
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/60 (0%) 2/59 (3.4%)
    Psychiatric disorders
    Anxiety 0/60 (0%) 0 1/59 (1.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/60 (0%) 0 1/59 (1.7%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Data or results obtained from this study must not be published without prior approval from the Sponsor.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Avillion LLP
    Phone +44 (0)203 764 9530
    Email avillion@avillionllp.com
    Responsible Party:
    Bond Avillion 2 Development LP
    ClinicalTrials.gov Identifier:
    NCT04234464
    Other Study ID Numbers:
    • AV005
    First Posted:
    Jan 21, 2020
    Last Update Posted:
    Jan 13, 2022
    Last Verified:
    Jan 1, 2022