A 12-week Study to Compare the Efficacy and Safety of Albuterol Spiromax® Versus a Placebo in People 12 Years and Older With Persistent Asthma

Study Overview
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Brief Summary
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The study will measure the change in lung function in subjects with asthma after inhaling from either of two inhalers: Albuterol Spiromax® or placebo.

Official Title
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A 12-week Comparison of the Efficacy and Safety of Albuterol Spiromax® Versus Placebo in Subjects 12 Years and Older With Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Placebo MDPI
* Drug: Albuterol MDPI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent/assent General good health Persistent asthma, with an FEV1 50-80% predicted. Ability to perform spirometry in an acceptable manner as per protocol guidelines. Ability to perform PEFR with a handheld peak flow meter. Demonstration of reversible bronchoconstriction as verified by a 15% or greater increase from baseline FEV1. Taking inhaled corticosteroids at a stable dose for at least 4 weeks prior to the Screening Visit. Non-smokers. Capable of understanding the requirements, risks, and benefits of study participation. Other inclusion criteria apply. Exclusion Criteria: Participation in any investigational drug trial within the 30 days preceding the Screening Visit (SV). A known hypersensitivity to albuterol or any of the excipients in the formulations. History of severe milk protein allergy. History of a respiratory infection or disorder that has not resolved within the 2 weeks preceding the Screening Visit (SV). Currently requires treatment with β2-adrenergic receptor antagonists or non-selective β-receptor blocking agents. History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation. Any asthma exacerbation requiring oral corticosteroids within 3 months of the Screening Visit (SV). A subject must not have had any hospitalization for asthma within 6 months prior to the Screening Visit (SV). Historical or current evidence of any clinically significant non-asthmatic acute or chronic condition including. Other exclusion 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo MDPI<br>Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks. | Drug: Placebo MDPI<br>* Placebo MDPI administered as 2 inhalations 4 times a day (QID) (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 12 weeks.<br>* Other names: Placebo Spiromax®;|
| Experimental: Albuterol MDPI<br>Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks. | Drug: Albuterol MDPI<br>* Albuterol MDPI administered as 2 inhalations 4 times a day (QID) (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 12 weeks.<br>* Other names: ProAir® RespiClick, Albuterol Spiromax®;|

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) Over the 12-week Treatment Period | FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average (by the trapezoidal rule) of FEV1 AUC 0-6 measures adjusted for the baseline measure (i.e., change from baseline at each timepoint) recorded on days 1, 8 and 85 of the treatment period. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min. | Day 1, Day 8 and Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 1 | 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 was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 1. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min. | Day 1 | 
| Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8 | 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 was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 8. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min. | Day 8 | 
| Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85 | 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 was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 85. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min. | Day 85 | 
| Participants With 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. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. 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 to Day 92 | 
| Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Physical exam was recorded as normal or abnormal based on physician assessment. Format for results is: Test Baseline/Endpoint HEENT = head, eyes, ears, nose, throat | Day 1 (Baseline), Day 85 | 
| Participants With Clinically Significant Vital Sign Assessments | For both standard and serial vital signs, participants were seated for at least 5 minutes before vital signs were assessed. Heart rate was obtained prior to the blood pressure measurement. Serial heart rate and blood pressure were conducted in the sitting position prior to the spirometry assessment; baseline measures were taken pre-dose at -30 ± 5 and -5 minutes on Day 1. Day 85 serial vital sign measures were taken in the sitting position prior to spirometry assessments pre-dose at -30 ± 5 and -5 minutes, then post-dose at 30 (±5) minutes, 1hr (± 10 min), 2hr (± 10 min), 3hr (± 10 min), 4hr (± 10 min), 5hr (± 10 min) and 6 hr (± 10 min). Serial heart rate and blood pressure measurements that were elevated to the following criteria were considered clinically significant: Systolic blood pressure: > 160 beats/minute Diastolic blood pressure: >100 beats/minute Heart rate: >120 beats/minute | Day 8, Day 85 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, dry powder inhaler, short-acting beta2-agonist, SABA, bronchoconstriction, bronchodilation, bronchodilator, metered dose inhaler