Asthma
Conditions
Brief summary
The purpose of this Phase II study is to evaluate efficacy and safety of inhaled formoterol fumarate in the Pressair DPI compared to the Foradil Aerolizer in patients with mild to moderate asthma. This study will include a screening visit followed by a 4 month treatment period.
Interventions
DRUGFormoterol Fumarate in the Pressair DPI, Low Dose
Formoterol Fumarate in the Pressair DPI 6 micrograms, twice a day for 14 days
DRUGFormoterol Fumarate in the Pressair DPI, High Dose
Formoterol Fumarate in the Pressair DPI 12 micrograms, twice a day for 14 days
DRUGForadil Aerolizer, Low Dose
Foradil Aerolizer 12 micrograms, twice a day for 14 days
DRUGForadil Aerolizer, High Dose
Foradil Aerolizer 24 micrograms, twice per day for 14 days
DRUGPlacebo
Placebo in the Pressair for 14 days
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusions: * Patients with mild-to-moderate asthma for at least 6 months prior to Visit 1 (as defined in the GINA Guidelines) which is unlikely to exacerbate during the study (e.g., due to seasonal allergen exposure). * Patients must be on a stable dose of Inhaled Corticosteroids (ICS) for at least 30 days prior to Visit 1. Patients on a combination of ICS/LABA must discontinue the use of LABA and must be on a stable dose of ICS for 30 days prior to Visit 1. * Qualifying spirometry at Visit 1 demonstrates highest FEV1 is ≤ 85% and ≥ 60% of predicted for age, height, and gender using NHANES III (NHANES 2010) when bronchodilator medications have been withheld the appropriate length of time per the List of Concomitant Medications (Appendix III) * Patient demonstrates reversibility with an increase in FEV1 of 12% and 200 mL after the administration of 360 µg of albuterol. * Highest pre-dose FEV1 at Visits 2, 4, 6, 8, and 10 must be within 25% of the qualifying FEV1 at Visit 1 Exclusions: * Patients with any clinically significant respiratory conditions other than mild to moderate asthma, such as COPD, active tuberculosis, or history of interstitial lung disease * Patients with a severe asthma exacerbation requiring hospitalization in the previous 12 months * Patient is not able to withhold use of inhaled short-acting beta-agonist (SABA) for at least 6 hours prior to visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) AUC0-6 After the Morning Dose (Day 14) | Baseline and up to 6 hrs post-dose (±15 min) on Day 14 of treatment | AUC0-6 is area under the curve from time 0 to 6 hours Serial spirometry was performed at -60 min predose, at 5 (+5) and 30 (±5) min post-dose, and at 1, 2, 3, 4, and 6 hrs post-dose (±15 min) Change from baseline was baseline of each treatment period The normalized FEV1 AUC0-6 was calculated by means of the trapezoidal method, dividing the area under the curve by the corresponding time intervals |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Normalized FEV1 AUC0-6 After the Morning Dose (Day 1) | Baseline and up to 6 hrs post-dose (±15 min) on Day 1 of treatment | AUC0-6 is area under the curve from time 0 to 6 hours Serial spirometry was performed at -60 min predose, at 5 (+5) and 30 (±5) min post-dose, and at 1, 2, 3, 4, and 6 hrs post-dose (±15 min) Change from baseline was baseline of Period 1 The time-normalized FEV1 AUC0-6 was calculated by means of the trapezoidal method, dividing the area under the curve by the corresponding time intervals |
Countries
United States
Participant flow
Recruitment details
The study was conducted in 29 study centers in the United States First patient visit was in June 2012 and last patient visit was in February 2013
Pre-assignment details
A total of 408 patients were screened; there were 234 screen failures, primarily (225/234) because inclusion/exclusion criteria were not met
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Population All patients participating in the crossover study | 174 |
| Total | 174 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Period 1 | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
| Period 1 | Sponsor request (potential unblinding) | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 2 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Period 2 | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0 |
| Period 3 | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 3 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Period 4 | Adverse Event | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 5 | Adverse Event | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Overall Study Population |
|---|---|
| Age, Continuous | 45.4 Years STANDARD_DEVIATION 13.2 |
| Gender Female | 91 Participants |
| Gender Male | 83 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 | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 167 | 2 / 163 | 2 / 164 | 1 / 166 | 0 / 165 |
| serious Total, serious adverse events | 0 / 167 | 2 / 163 | 0 / 164 | 0 / 166 | 0 / 165 |
Outcome results
Primary
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) AUC0-6 After the Morning Dose (Day 14)
AUC0-6 is area under the curve from time 0 to 6 hours Serial spirometry was performed at -60 min predose, at 5 (+5) and 30 (±5) min post-dose, and at 1, 2, 3, 4, and 6 hrs post-dose (±15 min) Change from baseline was baseline of each treatment period The normalized FEV1 AUC0-6 was calculated by means of the trapezoidal method, dividing the area under the curve by the corresponding time intervals
Time frame: Baseline and up to 6 hrs post-dose (±15 min) on Day 14 of treatment
Population: Intent to treat (ITT) Population defined as all patients in the Safety Population who had a baseline and at least 1 post-baseline FEV1 assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Foradil 24 μg | Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) AUC0-6 After the Morning Dose (Day 14) | 0.3196 Liters | Standard Error 0.0382 |
| Foradil 12 μg | Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) AUC0-6 After the Morning Dose (Day 14) | 0.3076 Liters | Standard Error 0.0382 |
| Formoterol 12 μg | Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) AUC0-6 After the Morning Dose (Day 14) | 0.2795 Liters | Standard Error 0.0382 |
| Formoterol 6 μg | Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) AUC0-6 After the Morning Dose (Day 14) | 0.2726 Liters | Standard Error 0.0381 |
| Placebo | Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) AUC0-6 After the Morning Dose (Day 14) | 0.0552 Liters | Standard Error 0.0382 |
p-value: <0.000195% CI: [0.2353, 0.2934]Mixed Models Analysis
p-value: <0.000195% CI: [0.2218, 0.283]Mixed Models Analysis
p-value: <0.000195% CI: [0.1941, 0.2544]Mixed Models Analysis
p-value: <0.000195% CI: [0.1887, 0.2461]Mixed Models Analysis
Secondary
Change From Baseline in Normalized FEV1 AUC0-6 After the Morning Dose (Day 1)
AUC0-6 is area under the curve from time 0 to 6 hours Serial spirometry was performed at -60 min predose, at 5 (+5) and 30 (±5) min post-dose, and at 1, 2, 3, 4, and 6 hrs post-dose (±15 min) Change from baseline was baseline of Period 1 The time-normalized FEV1 AUC0-6 was calculated by means of the trapezoidal method, dividing the area under the curve by the corresponding time intervals
Time frame: Baseline and up to 6 hrs post-dose (±15 min) on Day 1 of treatment
Population: Intent to treat (ITT) Population defined as all patients in the Safety Population who had a baseline and at least 1 post-baseline FEV1 assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Foradil 24 μg | Change From Baseline in Normalized FEV1 AUC0-6 After the Morning Dose (Day 1) | 0.3544 Liters | Standard Error 0.0196 |
| Foradil 12 μg | Change From Baseline in Normalized FEV1 AUC0-6 After the Morning Dose (Day 1) | 0.3068 Liters | Standard Error 0.0198 |
| Formoterol 12 μg | Change From Baseline in Normalized FEV1 AUC0-6 After the Morning Dose (Day 1) | 0.2712 Liters | Standard Error 0.0197 |
| Formoterol 6 μg | Change From Baseline in Normalized FEV1 AUC0-6 After the Morning Dose (Day 1) | 0.2204 Liters | Standard Error 0.0197 |
| Placebo | Change From Baseline in Normalized FEV1 AUC0-6 After the Morning Dose (Day 1) | 0.0306 Liters | Standard Error 0.0198 |