A Dose-ranging Study to Evaluate Albuterol and Hydrofluoroalkane in Subjects Ages 12 and Older With Persistent Asthma

Study Overview
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Brief Summary
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This study is examining how well a dry powder inhaler (DPI) of albuterol medication works to help adult and adolescent subjects 12 years of age and older with persistent asthma to improve lung function.

Official Title
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A Double-blind, Randomized, Placebo-controlled, 5-way Crossover, Multicenter, Single-dose, Dose-ranging Study to Compare the Efficacy and Safety of Albuterol Spiromax® and ProAir® HFA in Adult and Adolescent Subjects Ages 12 and Older With Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Albuterol Spiromax®
* Drug: ProAir® HFA
* Other: Placebo Inhaler


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must provide written informed consent, Be between 12 years of age and older, Male or Female, females of non-child bearing potential or using reliable contraception Asthma for at least 6 months, FEV1 (forced expiratory volume in 1 second) between 50-80% of predicted value, and reversibility greater than or equal to 15% following 180 mcg albuterol Stable low dose of Inhaled Corticosteroids Non-smoker, 12 months smoking-free and <=10-pack years history Otherwise healthy Other criteria apply Exclusion Criteria: Pregnant Allergic to albuterol or severe milk protein allergy Must not be on another trial for 30days. Other criteria apply

Ages Eligible for Study
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Minimum Age: 12 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: Albuterol Spiromax® 90 mcg<br>A single dose of albuterol 90 mcg delivered with Spiromax®, an inhalation-driven, multi-dose dry powder inhaler. Placebo inhalers used to maintain the blind. | Drug: Albuterol Spiromax®<br>* Albuterol Spiromax® delivers 90 mcg albuterol per inhalation. Doses of 180 mcg require two inhalations. Intervention given as double-blind medication on 2 of 5 treatment days, once at 90 mcg and once at 180 mcg.<br>* Other names: ProAir® RespiClick, Albuterol multi-dose dry powder inhaler (MDPI);Other: Placebo Inhaler<br>* Placebo delivered in both the Spiromax® and HFA inhalers to maintain the blind and also to support the placebo treatment arm.<br>|
| Experimental: Albuterol Spiromax® 180 mcg<br>A single dose of albuterol 180 mcg delivered with Spiromax®, an inhalation-driven, multi-dose dry powder inhaler (2 inhalations). Placebo inhalers used to maintain the blind. | Drug: Albuterol Spiromax®<br>* Albuterol Spiromax® delivers 90 mcg albuterol per inhalation. Doses of 180 mcg require two inhalations. Intervention given as double-blind medication on 2 of 5 treatment days, once at 90 mcg and once at 180 mcg.<br>* Other names: ProAir® RespiClick, Albuterol multi-dose dry powder inhaler (MDPI);Other: Placebo Inhaler<br>* Placebo delivered in both the Spiromax® and HFA inhalers to maintain the blind and also to support the placebo treatment arm.<br>|
| Active Comparator: ProAir® HFA 90 mcg<br>A single dose of albuterol 90 mcg delivered with ProAir®, a 'press-and-breathe', metered-dose, aerosol inhaler. Placebo inhalers used to maintain the blind. | Drug: ProAir® HFA<br>* ProAir® HFA delivers 90 mcg of albuterol per inhalation. Doses of 180 mcg require two inhalations. Intervention given as double-blind medication on 2 of 5 treatment days, once at 90 mcg and once at 180 mcg.<br>* Other names: albuterol HFA-MDI;Other: Placebo Inhaler<br>* Placebo delivered in both the Spiromax® and HFA inhalers to maintain the blind and also to support the placebo treatment arm.<br>|
| Active Comparator: ProAir® HFA 180 mcg<br>A single dose of albuterol 180 mcg delivered with ProAir®, a 'press-and-breathe', metered-dose, aerosol inhaler (2 inhalations). Placebo inhalers used to maintain the blind. | Drug: ProAir® HFA<br>* ProAir® HFA delivers 90 mcg of albuterol per inhalation. Doses of 180 mcg require two inhalations. Intervention given as double-blind medication on 2 of 5 treatment days, once at 90 mcg and once at 180 mcg.<br>* Other names: albuterol HFA-MDI;Other: Placebo Inhaler<br>* Placebo delivered in both the Spiromax® and HFA inhalers to maintain the blind and also to support the placebo treatment arm.<br>|
| Placebo Comparator: Placebo Inhaler<br>Placebo delivered with Spiromax®, an inhalation-driven, multi-dose dry powder inhaler, and with ProAir®, a 'press-and-breathe', metered-dose, aerosol inhaler. Placebo inhalers used to maintain the blind. | Other: Placebo Inhaler<br>* Placebo delivered in both the Spiromax® and HFA inhalers to maintain the blind and also to support the placebo treatment arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) | FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. The first baseline spirometry was obtained between 6-11 AM. The highest FEV1 value from two acceptable values was captured for calculation of the efficacy endpoints. Assessments were obtained at approximately 0.5 hours and immediately before dosing, and 5 minutes, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5 and 6 hours after completion of dosing. | Day 1 up to Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline-adjusted Percent-Predicted Forced Expiratory Volume in 1 Second (PPFEV1) Area Under the Curve (AUC 0-6) | Percent-predicted FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. Percent-predicted FEV1 is the expected FEV1 taking into account age, height, gender and race, as per the National Health and Nutrition Examination Survey III (NHANES III) reference values. The first baseline spirometry was obtained between 6-11 AM. The highest FEV1 value from two acceptable values was captured for calculation of the efficacy endpoints. Assessments were obtained at approximately 0.5 hours and immediately before dosing, and 5 minutes, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5 and 6 hours after completion of dosing. | Day 1 up to Day 30 | 
| Participants With Treatment-Emergent Adverse Events | Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes. | Day 1 up to Day 37 |