Asthma, Bronchospasm, Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
asthma, bronchospasm, COPD, reversibility, efficacy
Brief summary
The main objective is to evaluate the bronchodilatory efficacy, safety and pharmacokinetic profiles of A006 (Albuterol Dry Powder Inhaler (DPI)), in comparison with those of an active control, Proventil-HFA (Albuterol Metered Dose Inhaler (MDI)), and a Placebo DPI in escalating and cumulative-doses up to 1440 mcg, eight (8) times of the proposed clinical dose.
Interventions
DRUGA006
Albuterol DPI with 180 mcg Albuterol/inhalation
DRUGPlacebo DPI
Placebo DPI with 0 mcg Albuterol/inhalation
DRUGProventil-HFA
Albuterol MDI with 90 mcg Albuterol/inhalation
Sponsors
Amphastar Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Body weight ≥ 50 kg for men and ≥ 45 kg for women, and BMI within the range of 18.5 - 30.0 kg/m2 inclusive; * Sitting blood pressure ≤ 135/90 mmHg; * Demonstrating negative alcohol/drug screen tests; * Demonstrating negative HIV, HBsAg and HCV-Ab screen tests; * With mild-to-moderate persistent asthma for at least 6 months prior to Screening, and having used inhaled β-agonist(s) for asthma control; * Demonstrating a Mean Screening Baseline FEV1 at 50.0 - 85.0 % of predicted normal; * Demonstrating a ≥ 15.0% Airway Reversibility in FEV1 within 30(±5) min after inhaling 2 actuations of Proventil-HFA; * Demonstrating Peak Inspiratory Flow Rate within 80-150 L/min; * Demonstrating proficiency in the use of DPI and MDI after training; * Females of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control; * Having properly consented to participate in the trial.
Exclusion criteria
* Smoking history of ≥ 10 pack-years, or having smoked within 6 months prior to Screening; * Upper respiratory tract infections within 2 wk, or lower respiratory tract infection within 4 wk; * Asthma exacerbations that required emergency care or hospitalized treatment, within 4 wk prior; * Any current or recent respiratory conditions that might significantly affect pharmacodynamic response to the study drugs, besides asthma; * Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignancies, or other illnesses that could impact on the conduct, safety and evaluation of the study; * Known intolerance or hypersensitivity to any of the ingredients of the A006 or Proventil-HFA; * Use of prohibited drugs or failure to observe the drug washout restrictions; * Having been on other clinical drug/device studies in the last 30 days; * Having donated blood within the last 30 days prior to Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bronchodilatory efficacy after the escalating and cumulative-doses, up to 1,440 mcg. | -15 min predose, 15 min post dose 1, 2 and 3 and 15, 45, 90, 120, 180, 240, 360 min post dose 4 | Area Under the Curve (AUC)0-t of percent change in Forced Expiratory Volume in 1 second (FEV1), which is defined as the area under curve of post-dose FEV1 percentage changes from the Pre-dose Baseline FEV1 (FEV10) versus time. Doses are at 0, 30, 60 and 90 min. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to onset | 0 - 120 min | Time to onset of bronchodilatory effect, determined by linear interpolation as the point where FEV1 % change first reaches ≥ 12% from FEV10. |
| Peak Response | 15 min post dose 1, 2 and 3 and 15, 45, 90, 120, 180, 240, and 360 min post dose 4 | The peak bronchodilator response, defined as the maximum post-dose FEV1 % change. Doses are at time 0, 30, 60, and 90 min. |
| AUC0-t of change in FEV1 | -15, 15 min post 1, 2, and 3, and 15, 90, 120, 240, and 360min post dose 4 | AUC of FEV1 volume post-dose changes (change in Volume) from the Pre-dose Baseline FEV1 (FEV10). Doses are at 0, 30, 60 and 90 min. |
| Blood Analysis | -15, 10, 25,40, 55, 70, 85, 95, 115, 145, 175, 210, 270, 330, 690 min post dose 1 | serum glucose and potassium analysis and PK analysis |
| Vital Signs and Electrocardiogram (ECG) | -15, 5, 35, 65, 100, 155, 275, 455, 815 min post dose 1 | vital signs, including pulse and blood pressure and 12-lead ECG |
| Adverse Events | Time 0, 15, 45, 75, 105, 150, 195, 130, 190, 250, 435 minutes post dose 1 | The adverse drug events (ADE) that are observed with Proventil-HFA may be expected with the use of A006 |
Countries
United States
Outcome results
None listed