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

• Change in FEV1 Area Under the Curve (AUC) versus placebo [ Time Frame: Visits 1-7, at baseline, 5, 20, 30, 60, 90, 120, 240, 360 minutes post-dose ] [ Designated as safety issue: No ]
  Serial FEV1 measurements to demonstrate the mean AUC change in percent FEV1 from same-day baseline of A006 versus placebo control
  
  

• Placebo AUC of adjusted FEV1 changes [ Time Frame: Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose ] [ Designated as safety issue: No ]
  Determination of change of FEV1 in placebo arm
  
  
• AUC of post-dose FEV1 volume changes from pre-dose baseline to Visit 7 [ Time Frame: Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose ] [ Designated as safety issue: No ]
  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 [ Time Frame: Visits 1-7, at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose ] [ Designated as safety issue: No ]
  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) [ Time Frame: Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose ] [ Designated as safety issue: No ]
  The peak bronchodilator response (Fmax), defined as the maximum post-dose change in FEV1 percent.
  
  
• Time to peak FEV1 effect (tmax) [ Time Frame: Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose ] [ Designated as safety issue: No ]
  The time to peak FEV1 effect (tmax), defined as the time of Fmax.
  
  
• Duration of effect [ Time Frame: Visits 1-7 at 5, 20, 30, 60, 90, 120, 180 and 360 minutes post-dose ] [ Designated as safety issue: No ]
  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) [ Time Frame: Visits 1-7 at 60 minutes ] [ Designated as safety issue: No ]
  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 [ Time Frame: Visits 1-7 ] [ Designated as safety issue: No ]
  Evaluation of change in FEV1 in relation to dose.
  
  
• Vital Signs (i.e.: blood pressure and heart rate) [ Time Frame: Visits 1-7 and EOS at baseline, 3, 8, 15, 30, 90 and 360 minutes post-dose ] [ Designated as safety issue: Yes ]
  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) [ Time Frame: Visits 1-7 at baseline, 10, 50 and 360 minutes post-dose ] [ Designated as safety issue: Yes ]
  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 [ Time Frame: Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose ] [ Designated as safety issue: Yes ]
  Determination of Serum glucose, at pre-dose baseline, and at 15, 35 and 120 min post-dose.
  
  
• Serum potassium [ Time Frame: Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose ] [ Designated as safety issue: Yes ]
  Determination of serum potassium levels, at pre-dose baseline, and at 15, 35 and 120 min post-dose.
  
  
• Asthma exacerbation incidents [ Time Frame: Visits 1-7 and EOS ] [ Designated as safety issue: Yes ]
  Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study.
  
  
• Asthma management/ rescue drug usage [ Time Frame: Visits 1-7 and EOS ] [ Designated as safety issue: Yes ]
  Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study.
  
  
• Physical examination [ Time Frame: Screening and End-of-Study Visit ] [ Designated as safety issue: Yes ]
  Physical examination of all subjects performed at screening and end-of-study visit to evaluate subject's general health.
  
  
• CBC [ Time Frame: Screening and End-of-Study Visit ] [ Designated as safety issue: Yes ]
  Evaluation of CBC in all subjects at screening and end-of-study visit.
  
  
• Comprehensive metabolic panel [ Time Frame: Screening and End-of-Study Visit ] [ Designated as safety issue: Yes ]
  Comprehensive metabolic panel performed on all subjects at screening and end-of-study visit.
  
  
• Urinalysis [ Time Frame: Screening and End-of-Study Visit ] [ Designated as safety issue: Yes ]
  Urinalysis performed on all subjects at screening and end-of-study visit.
  
  
• Pregnancy test [ Time Frame: Screening and End-of-Study Visit ] [ Designated as safety issue: Yes ]
  A pregnancy test for women of child bearing potential at screening and end-of-study visit.
  
  
• Medication interactions [ Time Frame: Screening, Visits 1-7 and End-of-Study Visit ] [ Designated as safety issue: Yes ]
  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 [ Time Frame: Screening, Visits 1-7, End-of-Study Visit ] [ Designated as safety issue: Yes ]
  Adverse drug events whether observed by investigators or reported by subjects, will be documented, evaluated, followed up, and treated if deemed necessary.
  
  

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.