Asthma
Conditions
Brief summary
This is a randomized, cumulative dose, open-label, 2-period crossover, multi-center study to assess the safety, efficacy, PK, and extrapulmonary PD of cumulative doses of AS MDI compared to cumulative doses of Proventil as an active control in subjects with mild to moderate asthma
Detailed description
This is a randomized, cumulative dose, open-label, 2-period crossover, multi-center study to assess the safety, efficacy, PK, and extrapulmonary pharmacodynamics (PD) of cumulative doses of Albuterol Sulfate Pressurized Inhalation Suspension (hereafter referred to as AS MDI) compared to cumulative doses of Proventil® hydrofluoroalkane (HFA; hereafter referred to as Proventil) as an active control in subjects with mild to moderate asthma.
Interventions
DRUGAS MDI
AS MDI 1+1+2+4+8 inhalations of 90 μg per inhalation
DRUGProventil
Proventil 1+1+2+4+8 inhalations of 90 μg per inhalation
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Have stable (for 6 months) physician-diagnosed asthma with historical documentation of the diagnosis * Must be receiving 1 of the following required inhaled asthma therapies listed below for at least the last 30 days; Only SABA, which is used as needed for rescue, or Low to medium doses of ICS (alone or in combination with LABA), used regularly as maintenance asthma therapy * Demonstrate acceptable spirometry performance (ie, meet American Thoracic Society \[ATS\]/European Respiratory Society \[ERS\] acceptability/repeatability criteria * Pre-bronchodilator FEV1 of ≥50 to \<80% predicted normal value after withholding SABA ≥6 hours * Confirmed FEV1 reversibility to Ventolin, defined as a post-Ventolin increase in FEV1 of ≥15% * Only 2 reversibility testing attempts are allowed
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) * Oral corticosteroid use (any dose) within 6 weeks * Received any marketed (eg, omalizumab, mepolizumab, reslizumab) or investigational biologic within 3 months or 5 half-lives, whichever is longer, or any other medication specifically prohibited by the protocol * Current smokers, former smokers with \>10 pack-years history, or former smokers who stopped smoking \<6 months (including all forms of tobacco, e-cigarettes \[vaping\], and marijuana) * Life-threatening asthma as defined as any history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s) * Historical or current evidence of a clinically significant disease * Cancer not in complete remission for at least 5 years * Hospitalized for psychiatric disorder or attempted suicide within 1 year * Unable to abstain from protocol-defined prohibited medications during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose | At the two study treatment visits, FEV1 (forced expiratory volume in 1 second) will be measured prior to drug administration and 5 times, once at 30 minutes after each of the 5 doses | Forced expiratory volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline-adjusted FEV1 AUC0-6 After the Last Cumulative Dose | Over 6 hours post dose on Day 1 | The baseline-adjusted FEV1 AUC0-6 is the area under the curve for change from baseline calculated using the trapezoidal rule and normalized by dividing the AUC by the length of follow up post the last cumulative dose (typically 6 hours) (spirometry will be obtained at 5, 15, 30, 45, 60, 120, 180, and 240 minutes post-dose) normalized for length of follow up). |
Countries
United States
Participant flow
Pre-assignment details
Subjects who met all screening and randomization requirements were eligible for rand to Tx Period, comprised of Visits 2 and 3 . Eligible subj were rand via IWRS to receive 2 cumulative-dose Tx's in one of 2 possible Tx sequences: AS MDI, given as 1+1+2+4+8 actuations of AS MDI 90 μg, Proventil, given as 1+1+2+4+8 actuations of Proventil 90 μg
Participants by arm
| Arm | Count |
|---|---|
| mITT Population The mITT Analysis Set is defined as a subset of the ITT Analysis Set including subjects who received treatment and had post-treatment efficacy data from both Treatment Periods. Data judged to be impacted by major protocol deviations are determined prior to database lock in a blinded fashion and excluded per the statistical protocol deviation plan. Statistical tabulations and analyses are by randomized treatment, but data obtained after subjects received an incorrect treatment are excluded from the affected periods | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | mITT Population |
|---|---|
| Age, Continuous | 34.2 Years STANDARD_DEVIATION 7.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 46 |
| other Total, other adverse events | 8 / 45 | 10 / 46 |
| serious Total, serious adverse events | 0 / 45 | 0 / 46 |
Outcome results
Primary
Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose
Forced expiratory volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation
Time frame: At the two study treatment visits, FEV1 (forced expiratory volume in 1 second) will be measured prior to drug administration and 5 times, once at 30 minutes after each of the 5 doses
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| AS MDI | Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose | Cumulative Dose - 1440 μg | 0.721 Liter |
| AS MDI | Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose | Cumulative Dose - 180 μg | 0.548 Liter |
| AS MDI | Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose | Dose 1 - 90 μg | 0.421 Liter |
| AS MDI | Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose | Cumulative Dose - 360 μg | 0.619 Liter |
| AS MDI | Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose | Cumulative Dose - 720 μg | 0.659 Liter |
| Proventil | Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose | Cumulative Dose - 360 μg | 0.647 Liter |
| Proventil | Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose | Cumulative Dose - 720 μg | 0.690 Liter |
| Proventil | Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose | Cumulative Dose - 1440 μg | 0.805 Liter |
| Proventil | Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose | Dose 1 - 90 μg | 0.488 Liter |
| Proventil | Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose | Cumulative Dose - 180 μg | 0.586 Liter |
Secondary
Baseline-adjusted FEV1 AUC0-6 After the Last Cumulative Dose
The baseline-adjusted FEV1 AUC0-6 is the area under the curve for change from baseline calculated using the trapezoidal rule and normalized by dividing the AUC by the length of follow up post the last cumulative dose (typically 6 hours) (spirometry will be obtained at 5, 15, 30, 45, 60, 120, 180, and 240 minutes post-dose) normalized for length of follow up).
Time frame: Over 6 hours post dose on Day 1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AS MDI | Baseline-adjusted FEV1 AUC0-6 After the Last Cumulative Dose | 0.561 Liter |
| Proventil | Baseline-adjusted FEV1 AUC0-6 After the Last Cumulative Dose | 0.602 Liter |