Asthma
Conditions
Brief summary
This is a randomized, double-blind, single-dose, placebo-controlled, 5-period, 5-treatment, crossover, multi-center study to assess the bronchodilatory effect and safety of 2 dose levels of Albuterol Sulfate Pressurized Inhalation Suspension (hereafter referred to as AS MDI), 90 μg and 180 μg, compared with placebo for AS MDI (hereafter referred to as Placebo MDI) and open-label Proventil® hydrofluoroalkane (HFA; hereafter referred to as Proventil) 90 μg and 180 μg in adult and adolescent subjects with mild to moderate asthma. This study design utilizes 10 treatment sequences.
Detailed description
This is a 5-period crossover study. Each Treatment Period is 1 day. Subjects will receive a single dose of randomized study drug at each of the 5 Treatment Visits (Visits 2, 3, 4, 5, and 6), with a 3- to 7-day Washout Period between Treatment Visits.
Interventions
DRUGAS MDI 90 μg
AS MDI 90 μg (2 actuations of 45 μg/actuation)
DRUGAS MDI 180 µg
AS MDI 180 μg (2 actuations of 90 μg/actuation)
OTHERPlacebo MDI
Placebo MDI (2 actuations)
DRUGProventil 90 μg
Proventil 90 μg (1 actuation of 90 μg/actuation)
DRUGProventil 180 μg
Proventil 180 μg (2 actuations of 90 μg/actuation)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Are at least 12 years of age and no older than 65 years * 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 ≥40 to \<90% predicted normal value after withholding SABA for ≥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 * 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 |
|---|---|---|
| Change From Baseline in FEV1 AUC0-6 | Over 6 hours post dose on Day 1 | Change from baseline in FEV1 (Forced expiratory volume in 1 second) AUC0-6 (Area under the curve from 0 to 6 hours) (spirometry will be obtained at 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose) normalized for length of follow up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FEV1 AUC0-4 | Over 4 hours post dose on Day 1 | Change from baseline in FEV1 (Forced expiratory volume in 1 second) AUC0-4 (Area under the curve from 0 to 4 hours) (spirometry will be obtained at 5, 15, 30, 45, 60, 120, 180, and 240 minutes post-dose) normalized for length of follow up. |
| Peak Change From Baseline in FEV1 | Over 6 hours post dose on Day 1 | Peak Change from baseline in FEV1 (Forced expiratory volume in 1 second) |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 10 sites in the United States, from December 2017 to March 2018. The study was anticipated to run for at least 23 days but not to exceed 68 days.
Pre-assignment details
Subjects were randomized into one of 10 treatment sequences. Each sequence comprised all 5 treatments included in this study (ie, AS MDI 90 μg, AS MDI 180 μg, Placebo MDI, Proventil 90 μg, and Proventil 180 μg) in a randomized order
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Safety Set | 86 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 42.7 Years STANDARD_DEVIATION 13.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 72 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 20 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 | 3 Participants |
| Race (NIH/OMB) White | 62 Participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 82 | 0 / 81 | 0 / 81 | 0 / 82 | 0 / 79 |
| other Total, other adverse events | 0 / 82 | 0 / 81 | 0 / 81 | 0 / 82 | 0 / 79 |
| serious Total, serious adverse events | 0 / 82 | 0 / 81 | 0 / 81 | 0 / 82 | 0 / 79 |
Outcome results
Primary
Change From Baseline in FEV1 AUC0-6
Change from baseline in FEV1 (Forced expiratory volume in 1 second) AUC0-6 (Area under the curve from 0 to 6 hours) (spirometry will be obtained at 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose) normalized for length of follow up.
Time frame: Over 6 hours post dose on Day 1
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AS MDI 180 µg | Change From Baseline in FEV1 AUC0-6 | 0.266 Liters |
| AS MDI 90 µg | Change From Baseline in FEV1 AUC0-6 | 0.203 Liters |
| Proventil 180 µg | Change From Baseline in FEV1 AUC0-6 | 0.282 Liters |
| Proventil 90 µg | Change From Baseline in FEV1 AUC0-6 | 0.240 Liters |
| Placebo MDI | Change From Baseline in FEV1 AUC0-6 | 0.070 Liters |
Secondary
Change From Baseline in FEV1 AUC0-4
Change from baseline in FEV1 (Forced expiratory volume in 1 second) AUC0-4 (Area under the curve from 0 to 4 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 4 hours post dose on Day 1
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AS MDI 180 µg | Change From Baseline in FEV1 AUC0-4 | 0.331 Liters |
| AS MDI 90 µg | Change From Baseline in FEV1 AUC0-4 | 0.263 Liters |
| Proventil 180 µg | Change From Baseline in FEV1 AUC0-4 | 0.349 Liters |
| Proventil 90 µg | Change From Baseline in FEV1 AUC0-4 | 0.297 Liters |
| Placebo MDI | Change From Baseline in FEV1 AUC0-4 | 0.080 Liters |
Secondary
Peak Change From Baseline in FEV1
Peak Change from baseline in FEV1 (Forced expiratory volume in 1 second)
Time frame: Over 6 hours post dose on Day 1
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AS MDI 180 µg | Peak Change From Baseline in FEV1 | 0.509 Liters |
| AS MDI 90 µg | Peak Change From Baseline in FEV1 | 0.433 Liters |
| Proventil 180 µg | Peak Change From Baseline in FEV1 | 0.516 Liters |
| Proventil 90 µg | Peak Change From Baseline in FEV1 | 0.472 Liters |
| Placebo MDI | Peak Change From Baseline in FEV1 | 0.233 Liters |