Asthma
Conditions
Keywords
asthma, mild-to-moderate persistent asthma, mild asthma, moderate asthma, persistent asthma
Brief summary
The main objective of this study is to evaluate the efficacy, dose-ranging and initial safety profiles of A006, an Albuterol dry powder inhaler (DPI), in the dose range of 25 to 180 mcg per dosing in comparison to a DPI Placebo Control and an Albuterol metered dose inhaler (MDI) Active Control. This study will be conducted in male and female adult patients who have mild-to-moderate persistent asthma for at least 6 months, but are otherwise generally healthy.
Detailed description
The main objective of this study is to evaluate the efficacy, dose-ranging and initial safety profiles of A006, an Albuterol dry powder inhaler (DPI), in the dose range of 25 to 180 mcg per dose in comparison to the DPI Placebo Control and the Active (Reference) Control. The study results of this study together with that of A006-B study will be utilized to determine the optimum final dose range of A006 for further clinical studies. The study will be conducted in male and female adult patients who have mild-to-moderate persistent asthma but are otherwise generally healthy.
Interventions
DRUGAlbuterol DPI 25 mcg/inh
Albuterol DPI with 25 mcg Albuterol/inhalation
DRUGAlbuterol DPI 90 mcg/inh
Albuterol DPI with 90 mcg Albuterol/inhalation
DRUGPlacebo DPI
Placebo DPI with 0 mcg Albuterol/inhalation
DRUGAlbuterol MDI 90 mcg/inh
Albuterol MDI with 90 mcg Albtuerol/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
* Generally healthy, male and female adults, 18-55 years of age at screening * With mild-to-moderate persistent asthma for at least 6 months prior to screening and having used a beta-agonist(s) inhaler * Demonstrate a Forced Expiratory Volume (FEV1) at 50-85 percent of predicted normal during screening baseline measurement * Demonstrate an airway reversibility of greater than or equal to 15 percent within 30 minutes of inhaling 2 inhalations of Proventil MDI during screening visit * Demonstrate Peak Inspiratory Flow Rate (PIF) within 80-150 L/min (after training), at least 2 times consecutively * Demonstrate ability to use a DPI and MDI inhaler properly after training * Females must be not pregnant, not lactating, and using a clinically acceptable form of birth control * Properly agree to participate in the trial
Exclusion criteria
* A smoking history of more than or equal to 10 years or having smoked within 6 months of screening visit * Upper respiratory tract infections within 2 weeks or lower respiratory tract infection within 4 weeks prior to screening visit * Asthma exacerbations that required emergency care or a hospital stay within 4 weeks prior to screening visit * Any current or recent respiratory tract infections that might affect the response to the study drug as determined by the investigator, including cystic fibrosis, bronchiectasis, tuberculosis, emphysema and other significant respiratory diseases besides asthma * Current clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignant or other illnesses that could impact the study as determined by the investigator * Known intolerance or hypersensitivity to any ingredients of the study drug DPI or Proventil MDI (i.e.: Albuterol, sulfate, lactose, milk protein, HFA-134a, oleic acid and ethanol)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in FEV1 Area Under the Curve (AUC) versus placebo | Visits 1-7, at baseline, 5, 20, 30, 60, 90, 120, 240, 360 minutes post-dose | Serial FEV1 measurements to demonstrate the mean AUC change in percent FEV1 from same-day baseline of A006 versus placebo control |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC of post-dose FEV1 volume changes from pre-dose baseline to Visit 7 | Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose | Determination of FEV1 volume change from pre-dose baseline to post treatment at Visit 7 |
| Time post-dose change in FEV1 percent first reaches greater than or equal to 12 percent over the Pre-dose Baseline | Visits 1-7, at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose | Time to onset of bronchodilator effect (Tonset), determined by linear interpolation as the point where post-dose change in FEV1 percent first reaches greater than or equal to 12 percent over the Pre-dose Baseline. |
| Peak bronchodilator response (Fmax) | Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose | The peak bronchodilator response (Fmax), defined as the maximum post-dose change in FEV1 percent. |
| Time to peak FEV1 effect (tmax) | Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose | The time to peak FEV1 effect (tmax), defined as the time of Fmax. |
| Duration of effect | Visits 1-7 at 5, 20, 30, 60, 90, 120, 180 and 360 minutes post-dose | Duration of effect, calculated as the total duration of bronchodilator effects when change in FEV1 percent is greater than or equal to 12 percent above baseline. |
| Bronchodilatory Response Rate (R percent) | Visits 1-7 at 60 minutes | Evaluation of Bronchodilatory Response Rate (R percent) of responders who demonstrate a greater than or equal to 12 percent increase for change in FEV1 percent during the initial 60 min post-dose. |
| Dose response curve: AUC of change in percent FEV1 versus Dose | Visits 1-7 | Evaluation of change in FEV1 in relation to dose. |
| Vital Signs (i.e.: blood pressure and heart rate) | Visits 1-7 and EOS at baseline, 3, 8, 15, 30, 90 and 360 minutes post-dose | Vital signs, i.e. blood pressure (SBP/DBP) and heart rate (HR), at pre-dose baseline, and 3, 8, 15, 30, 90, and 360 min post-dose. |
| 12-lead ECG (for routine and QT/QTc) | Visits 1-7 at baseline, 10, 50 and 360 minutes post-dose | Measurement of 12-lead ECG (for routine and QT/QTc), at pre-dose baseline, and at 10, 50, and 360 min post-dose. |
| Serum glucose | Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose | Determination of Serum glucose, at pre-dose baseline, and at 15, 35 and 120 min post-dose. |
| Placebo AUC of adjusted FEV1 changes | Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose | Determination of change of FEV1 in placebo arm |
| Asthma exacerbation incidents | Visits 1-7 and EOS | Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study. |
| Asthma management/ rescue drug usage | Visits 1-7 and EOS | Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study. |
| Physical examination | Screening and End-of-Study Visit | Physical examination of all subjects performed at screening and end-of-study visit to evaluate subject's general health. |
| CBC | Screening and End-of-Study Visit | Evaluation of CBC in all subjects at screening and end-of-study visit. |
| Comprehensive metabolic panel | Screening and End-of-Study Visit | Comprehensive metabolic panel performed on all subjects at screening and end-of-study visit. |
| Urinalysis | Screening and End-of-Study Visit | Urinalysis performed on all subjects at screening and end-of-study visit. |
| Pregnancy test | Screening and End-of-Study Visit | A pregnancy test for women of child bearing potential at screening and end-of-study visit. |
| Medication interactions | Screening, Visits 1-7 and End-of-Study Visit | Evaluation of concomitant medications used by subjects throughout the study and their potential to affect the study |
| Number of participants with adverse events as a measure of safety and tolerability | Screening, Visits 1-7, End-of-Study Visit | Adverse drug events whether observed by investigators or reported by subjects, will be documented, evaluated, followed up, and treated if deemed necessary. |
| Serum potassium | Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose | Determination of serum potassium levels, at pre-dose baseline, and at 15, 35 and 120 min post-dose. |
Countries
United States
Outcome results
None listed