Albuterol DPI (A006) Clinical Study-B2: Efficacy, Dose-Ranging and Initial Safety Evaluation

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double- or Evaluator-blind, Active- and Placebo-controlled, Single Dose, Seven-arm, Crossover Dose-ranging Study of A006 in Adult Asthma Patients

Conditions
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Asthma

Intervention / Treatment
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* Drug: Albuterol DPI 25 mcg/inh
* Drug: Albuterol DPI 90 mcg/inh
* Drug: Placebo DPI
* Drug: Albuterol MDI 90 mcg/inh


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T1<br>Two inhalations, one of Albuterol DPI 25 mcg/inh and one of Placebo DPI; Total Albuterol dose of 25 mcg | Drug: Albuterol DPI 25 mcg/inh<br>* Albuterol DPI with 25 mcg Albuterol/inhalation<br>Drug: Placebo DPI<br>* Placebo DPI with 0 mcg Albuterol/inhalation<br>|
| Experimental: T2<br>Two inhalations of Albuterol DPI 25 mcg/inh; Total Albuterol dose of 50 mcg | Drug: Albuterol DPI 25 mcg/inh<br>* Albuterol DPI with 25 mcg Albuterol/inhalation<br>|
| Experimental: T3<br>Two inhalations, one of Albuterol DPI 90 mcg/inh and one of Placebo DPI; Total Albuterol dose of 90 mcg | Drug: Albuterol DPI 90 mcg/inh<br>* Albuterol DPI with 90 mcg Albuterol/inhalation<br>Drug: Placebo DPI<br>* Placebo DPI with 0 mcg Albuterol/inhalation<br>|
| Experimental: T4<br>Two inhalations of Albuterol DPI 90 mcg/inh; Total Albuterol dose of 180 mcg | Drug: Albuterol DPI 90 mcg/inh<br>* Albuterol DPI with 90 mcg Albuterol/inhalation<br>|
| Placebo Comparator: P<br>Two inhalations Placebo DPI; Total Albuterol dose of 0 mcg | Drug: Placebo DPI<br>* Placebo DPI with 0 mcg Albuterol/inhalation<br>|
| Active Comparator: R1<br>One inhalation of Albuterol MDI 90 mcg/inh; Total Albuterol dose of 90 mcg | Drug: Albuterol MDI 90 mcg/inh<br>* Albuterol MDI with 90 mcg Albtuerol/inhalation<br>|
| Active Comparator: R2<br>Two inhalations of Albuterol MDI 90 mcg/inh; Total Albuterol dose of 180 mcg | Drug: Albuterol MDI 90 mcg/inh<br>* Albuterol MDI with 90 mcg Albtuerol/inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FEV1 Area Under the Curve (AUC) versus placebo | Serial FEV1 measurements to demonstrate the mean AUC change in percent FEV1 from same-day baseline of A006 versus placebo control | Visits 1-7, at baseline, 5, 20, 30, 60, 90, 120, 240, 360 minutes post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Placebo AUC of adjusted FEV1 changes | Determination of change of FEV1 in placebo arm | Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose | 
| AUC of post-dose FEV1 volume changes from pre-dose baseline to Visit 7 | Determination of FEV1 volume change from pre-dose baseline to post treatment at Visit 7 | Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose | 
| Time post-dose change in FEV1 percent first reaches greater than or equal to 12 percent over the Pre-dose Baseline | 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. | Visits 1-7, at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose | 
| Peak bronchodilator response (Fmax) | The peak bronchodilator response (Fmax), defined as the maximum post-dose change in FEV1 percent. | Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose | 
| Time to peak FEV1 effect (tmax) | The time to peak FEV1 effect (tmax), defined as the time of Fmax. | Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose | 
| Duration of effect | 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. | Visits 1-7 at 5, 20, 30, 60, 90, 120, 180 and 360 minutes post-dose | 
| Bronchodilatory Response Rate (R percent) | 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. | Visits 1-7 at 60 minutes | 
| Dose response curve: AUC of change in percent FEV1 versus Dose | Evaluation of change in FEV1 in relation to dose. | Visits 1-7 | 
| Vital Signs (i.e.: blood pressure and heart rate) | 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. | Visits 1-7 and EOS at baseline, 3, 8, 15, 30, 90 and 360 minutes post-dose | 
| 12-lead ECG (for routine and QT/QTc) | Measurement of 12-lead ECG (for routine and QT/QTc), at pre-dose baseline, and at 10, 50, and 360 min post-dose. | Visits 1-7 at baseline, 10, 50 and 360 minutes post-dose | 
| Serum glucose | Determination of Serum glucose, at pre-dose baseline, and at 15, 35 and 120 min post-dose. | Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose | 
| Serum potassium | Determination of serum potassium levels, at pre-dose baseline, and at 15, 35 and 120 min post-dose. | Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose | 
| Asthma exacerbation incidents | Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study. | Visits 1-7 and EOS | 
| Asthma management/ rescue drug usage | Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study. | Visits 1-7 and EOS | 
| Physical examination | Physical examination of all subjects performed at screening and end-of-study visit to evaluate subject's general health. | Screening and End-of-Study Visit | 
| CBC | Evaluation of CBC in all subjects at screening and end-of-study visit. | Screening and End-of-Study Visit | 
| Comprehensive metabolic panel | Comprehensive metabolic panel performed on all subjects at screening and end-of-study visit. | Screening and End-of-Study Visit | 
| Urinalysis | Urinalysis performed on all subjects at screening and end-of-study visit. | Screening and End-of-Study Visit | 
| Pregnancy test | A pregnancy test for women of child bearing potential at screening and end-of-study visit. | Screening and End-of-Study Visit | 
| Medication interactions | Evaluation of concomitant medications used by subjects throughout the study and their potential to affect the study | Screening, Visits 1-7 and End-of-Study Visit | 
| Number of participants with adverse events as a measure of safety and tolerability | Adverse drug events whether observed by investigators or reported by subjects, will be documented, evaluated, followed up, and treated if deemed necessary. | Screening, Visits 1-7, End-of-Study Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, mild-to-moderate persistent asthma, mild asthma, moderate asthma, persistent asthma