Asthma
Conditions
Keywords
Asthma and Poor Coordinators of Asthma Inhalers
Brief summary
This is a research study designed to compare the single-dose efficacy of albuterol-hydrofluoroalkane-breath-actuated inhaler (HFA-BAI) and albuterol-HFA-metered-dose inhaler (MDI) in asthmatics with poor inhaler coordinating abilities.
Interventions
DRUGAlbuterol-HFA-MDI
Inhalation Aerosols, 90 mcg, 1 dose per treatment period
DRUGAlbuterol-HFA-BAI
Inhalation Aerosol (Breath-Actuated), 90 mcg, 1 dose per treatment period.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Asthma of a minimum of 6 months duration * Participants who demonstrate poor inhalation/actuation coordination when evaluated at screening utilizing the Aerosol Inhalation Monitor (AIM, Vitalograph) prior to any training and following training in 3 consecutive attempts * Reversible bronchoconstriction of \>12% increase in FEV1 with a cumulative dose of 450 mcg of albuterol * The reversibility (FEV1) of ≤70% following administration of the initial 90 mcg of albuterol * Ability to perform spirometry reproducibly * Ability to self-perform peak expiratory flow (PEF) determinations and report scores on diaries * Can tolerate withdrawal of applicable medications for qualification at screening * Otherwise healthy individuals * Non-smokers for at least 2 years prior to the screening visit
Exclusion criteria
* Allergy or sensitivity to albuterol * Exposure to investigational drugs within 30 days prior to the screening visit * Continuous treatment with beta-blockers, monoamine oxidase (MAO) inhibitors, tricyclic antidepressants, and/or systemic corticosteroids * Treated with oral or injectable corticosteroids within the 6 weeks prior to the screening visit * The prescribed dose regimen of any required antileukotrienes, inhaled corticosteroids and/or inhaled cromolyn and/or nedocromil had not been stable for at least 4 weeks prior to the screening visit * Inability to tolerate or unwillingness to comply with required washout periods for all applicable medications * Hospitalization for acute exacerbation of asthma more than twice in past year * Treatment in an emergency room or hospitalization for asthmatic symptoms within 3 months prior to the screening visit * An upper respiratory tract infection and/or sinusitis associated with exacerbation of asthma that is unresolved 3 weeks prior to the screening visit * History and/or presence of any clinically significant non-asthmatic acute or chronic disease * Known or suspected substance abuse * Previous enrollment in an IVAX Research-sponsored Albuterol-HFA asthma study Note: Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area-Under-the-Effect Curve of Percent Change in Test-Day Baseline Forced Expiratory Volume in 1 Second (FEV1) Versus Time (up to 2 Hours Postdose), %FEV1 AUEC0-2 | Baseline, Up to 2 hours postdose | The %FEV1 AUEC0-2 was calculated using the linear trapezoidal rule. The baseline value consisted of the average of the two predose FEV1 measurements. The mean was obtained from the mixed-effect analysis of variance adjusted for effects from the study center, the treatment sequence, and study period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in FEV1 up to 2 Hours Postdose | Baseline up to 2 hours postdose | The mean was obtained from the mixed-effect analysis of variance adjusted for effects from the study center, the treatment sequence, and study period. |
| Area-Under-the-Effect Curve of Change in Test-Day Baseline FEV1 Versus Time (up to 2 Hours Postdose), FEV1 AUEC0-2 | Baseline up to 2 hours postdose | The %FEV1 AUEC0-2 was calculated using the linear trapezoidal rule. The test-day baseline consisted of the average of the two predose FEV1 measurements. The mean was obtained from the mixed-effect analysis of variance adjusted for effects from the study center, the treatment sequence, and study period. |
| Percentage of Participants With a 12% Increase From Baseline in FEV1 Within 2 Hours Postdose | Baseline up to 2 hours postdose | — |
| Percent Change From Baseline in FEV1 Within 30 Minutes Postdose | Baseline up to 30 minutes postdose | The mean was obtained from the mixed-effect analysis of variance adjusted for effects from the study center, the treatment sequence, and study period. |
| Time to a 12% Increase From Baseline in FEV1 Within 2 Hours Postdose | Baseline up to 2 hours postdose | The number of minutes required for the baseline FEV1 to increase by at least 12% within the 2-hour observation period. Median time and corresponding confidence intervals (CIs) were obtained via the Kaplan-Meier estimate. |
| Time to a 15% Increase From Baseline in FEV1 Within 2 Hours Postdose | Baseline up to 2 hours postdose | The number of minutes required for the baseline FEV1 to increase by at least 15% within the 2-hour observation period. Median time and corresponding CIs were obtained via the Kaplan-Meier estimate. |
| Time to Maximum Increase in FEV1 | Baseline up to 2 hours postdose | Each calculation for FEV1 took several minutes in order to obtain the highest of 3 measurements. The total collection time exceeded the 120 mins post-dose time frame for some participants. |
| Percentage of Participants With a 15% Increase From Baseline in FEV1 Within 2 Hours Postdose | Baseline up to 2 hours postdose | — |
Countries
United States
Participant flow
Pre-assignment details
Eligible participants were randomized to receive the following 2 treatments on separate occasions 2-7 days apart: Albuterol-hydrofluoroalkane-breath-actuated inhaler (HFA-BAI) and Albuterol-HFA-metered-dose inhaler (MDI).
Participants by arm
| Arm | Count |
|---|---|
| Overall Population Participants received single actuation of albuterol 90 mcg, administered using BAI in treatment period 1, then single actuation of albuterol 90 mcg, administered using MDI in treatment period 2. There was a washout period of 2-7 days between treatments. | 49 |
| Total | 49 |
Baseline characteristics
| Characteristic | Overall Population |
|---|---|
| Age, Continuous | 14.1 years STANDARD_DEVIATION 9.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Race Black or African heritage | 2 Participants |
| Race/Ethnicity, Customized Race White | 47 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 49 |
| other Total, other adverse events | 0 / 49 | 0 / 49 |
| serious Total, serious adverse events | 0 / 49 | 0 / 49 |
Outcome results
Primary
Area-Under-the-Effect Curve of Percent Change in Test-Day Baseline Forced Expiratory Volume in 1 Second (FEV1) Versus Time (up to 2 Hours Postdose), %FEV1 AUEC0-2
The %FEV1 AUEC0-2 was calculated using the linear trapezoidal rule. The baseline value consisted of the average of the two predose FEV1 measurements. The mean was obtained from the mixed-effect analysis of variance adjusted for effects from the study center, the treatment sequence, and study period.
Time frame: Baseline, Up to 2 hours postdose
Population: ITT population included all randomized participants who took at least 1 dose of the assigned study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Albuterol-HFA-BAI | Area-Under-the-Effect Curve of Percent Change in Test-Day Baseline Forced Expiratory Volume in 1 Second (FEV1) Versus Time (up to 2 Hours Postdose), %FEV1 AUEC0-2 | 21.403 percent change from baseline*hour | Standard Error 2.263 |
| Albuterol-HFA-MDI | Area-Under-the-Effect Curve of Percent Change in Test-Day Baseline Forced Expiratory Volume in 1 Second (FEV1) Versus Time (up to 2 Hours Postdose), %FEV1 AUEC0-2 | 20.457 percent change from baseline*hour | Standard Error 2.253 |
Comparison: The analysis was performed using the mixed-effect analysis of variance with fixed effects of center, sequence, treatment group and period, and random effect of the participant within sequence.p-value: 0.559595% CI: [-2.293, 4.185]ANCOVA
Secondary
Area-Under-the-Effect Curve of Change in Test-Day Baseline FEV1 Versus Time (up to 2 Hours Postdose), FEV1 AUEC0-2
The %FEV1 AUEC0-2 was calculated using the linear trapezoidal rule. The test-day baseline consisted of the average of the two predose FEV1 measurements. The mean was obtained from the mixed-effect analysis of variance adjusted for effects from the study center, the treatment sequence, and study period.
Time frame: Baseline up to 2 hours postdose
Population: ITT population included all randomized participants who took at least 1 dose of the assigned study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Albuterol-HFA-BAI | Area-Under-the-Effect Curve of Change in Test-Day Baseline FEV1 Versus Time (up to 2 Hours Postdose), FEV1 AUEC0-2 | 0.443 liters*hours | Standard Error 0.044 |
| Albuterol-HFA-MDI | Area-Under-the-Effect Curve of Change in Test-Day Baseline FEV1 Versus Time (up to 2 Hours Postdose), FEV1 AUEC0-2 | 0.407 liters*hours | Standard Error 0.044 |
Secondary
Percentage of Participants With a 12% Increase From Baseline in FEV1 Within 2 Hours Postdose
Time frame: Baseline up to 2 hours postdose
Population: ITT population included all randomized participants who took at least 1 dose of the assigned study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albuterol-HFA-BAI | Percentage of Participants With a 12% Increase From Baseline in FEV1 Within 2 Hours Postdose | 57.1 percentage of participants |
| Albuterol-HFA-MDI | Percentage of Participants With a 12% Increase From Baseline in FEV1 Within 2 Hours Postdose | 42.9 percentage of participants |
Secondary
Percentage of Participants With a 15% Increase From Baseline in FEV1 Within 2 Hours Postdose
Time frame: Baseline up to 2 hours postdose
Population: ITT population included all randomized participants who took at least 1 dose of the assigned study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albuterol-HFA-BAI | Percentage of Participants With a 15% Increase From Baseline in FEV1 Within 2 Hours Postdose | 32.7 percentage of participants |
| Albuterol-HFA-MDI | Percentage of Participants With a 15% Increase From Baseline in FEV1 Within 2 Hours Postdose | 30.6 percentage of participants |
Secondary
Percent Change From Baseline in FEV1 up to 2 Hours Postdose
The mean was obtained from the mixed-effect analysis of variance adjusted for effects from the study center, the treatment sequence, and study period.
Time frame: Baseline up to 2 hours postdose
Population: ITT population included all randomized participants who took at least 1 dose of the assigned study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Albuterol-HFA-BAI | Percent Change From Baseline in FEV1 up to 2 Hours Postdose | 14.319 percent change | Standard Error 1.292 |
| Albuterol-HFA-MDI | Percent Change From Baseline in FEV1 up to 2 Hours Postdose | 13.731 percent change | Standard Error 1.286 |
Secondary
Percent Change From Baseline in FEV1 Within 30 Minutes Postdose
The mean was obtained from the mixed-effect analysis of variance adjusted for effects from the study center, the treatment sequence, and study period.
Time frame: Baseline up to 30 minutes postdose
Population: ITT population included all randomized participants who took at least 1 dose of the assigned study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Albuterol-HFA-BAI | Percent Change From Baseline in FEV1 Within 30 Minutes Postdose | 10.777 percent change | Standard Error 1.185 |
| Albuterol-HFA-MDI | Percent Change From Baseline in FEV1 Within 30 Minutes Postdose | 10.114 percent change | Standard Error 1.18 |
Secondary
Time to a 12% Increase From Baseline in FEV1 Within 2 Hours Postdose
The number of minutes required for the baseline FEV1 to increase by at least 12% within the 2-hour observation period. Median time and corresponding confidence intervals (CIs) were obtained via the Kaplan-Meier estimate.
Time frame: Baseline up to 2 hours postdose
Population: ITT population included all randomized participants who took at least 1 dose of the assigned study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Albuterol-HFA-BAI | Time to a 12% Increase From Baseline in FEV1 Within 2 Hours Postdose | 60.00 minutes |
| Albuterol-HFA-MDI | Time to a 12% Increase From Baseline in FEV1 Within 2 Hours Postdose | NA minutes |
Secondary
Time to a 15% Increase From Baseline in FEV1 Within 2 Hours Postdose
The number of minutes required for the baseline FEV1 to increase by at least 15% within the 2-hour observation period. Median time and corresponding CIs were obtained via the Kaplan-Meier estimate.
Time frame: Baseline up to 2 hours postdose
Population: ITT population included all randomized participants who took at least 1 dose of the assigned study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Albuterol-HFA-BAI | Time to a 15% Increase From Baseline in FEV1 Within 2 Hours Postdose | NA minutes |
| Albuterol-HFA-MDI | Time to a 15% Increase From Baseline in FEV1 Within 2 Hours Postdose | NA minutes |
Secondary
Time to Maximum Increase in FEV1
Each calculation for FEV1 took several minutes in order to obtain the highest of 3 measurements. The total collection time exceeded the 120 mins post-dose time frame for some participants.
Time frame: Baseline up to 2 hours postdose
Population: ITT population included all randomized participants who took at least 1 dose of the assigned study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Albuterol-HFA-BAI | Time to Maximum Increase in FEV1 | 48.00 minutes |
| Albuterol-HFA-MDI | Time to Maximum Increase in FEV1 | 45.00 minutes |