A Twelve Month Long Term Safety Study to Evaluate the Safety of Albuterol in a Dry Powder Inhaler With Both Repeated and as Needed Dosing

Study Overview
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Brief Summary
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This is a one-year study to look at the safety of a dry powder inhaler with albuterol. After a one-week run in, for the first 3 months subjects will use an inhaler with either albuterol or a dummy drug at regular times four times a day. Then for the last nine months of the study, all subjects will be given the albuterol dry powder inhaler and will use it only when needed to help with breathing problems. Subjects will need to keep a daily diary (both paper and electronic) throughout the study recording any inhaler use and health problems. There will be visits to the study doctor about once a month for a year. This study is intended to show that the albuterol dry powder inhaler works well and is safe for use over a long period of time.

Detailed Description
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The Sponsor terminated this study due to the need for a modification to the Spiromax device utilized in this study; the problem identified has no impact on patient safety. Exposure ranged from 3 to 49 days with the majority of subjects receiving ≤30 days of double-blind treatment.

Official Title
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A Multi-Center 52-Week Study to Assess the Safety of an Albuterol Dry-powder Inhaler in Subjects With Asthma

Conditions
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Asthma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented history of persistent asthma with rescue use of albuterol on average of at least once/ week over the 4-weeks prior to screening. Female subjects who are of childbearing potential (as judged by the investigator) must be currently using and willing to continue to use a medically reliable method of contraception for the entire study duration General good health Capable of understanding the requirements, risks, and benefits of study participation Non-smoker for at least one year prior to the screening visit and a maximum pack-year smoking history of 10 years Other criteria apply Exclusion Criteria: Pregnancy, nursing, or plans to become pregnant or donate gametes (ova or sperm) for in vitro fertilization during the study period or for 30 days following the subject's last study related visit Participation in any investigational drug trial within 30 days preceding the screening visit 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 (including, but not limited to bronchitis, pneumonia, acute or chronic sinusitis, otitis media, influenza, etc) which is not resolved within 1 week prior to the Screening Visit. Use of any protocol prohibited concomitant medications for asthma or any protocol prohibited concomitant non-asthma medications Inability to tolerate or unwillingness to comply with the protocol requirements. History of life-threatening asthma Any asthma exacerbation within 3 months of the Screening Visit requiring oral or systemic corticosteroids History of life-threatening asthma 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Albuterol Spiromax<br>Albuterol multi-dose dry powder inhaler (Spiromax) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they take albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN). | Drug: Albuterol Spiromax<br>* Albuterol as a dry-powder inhaled orally using the Spiromax inhaler. Each inhalation delivers 90 micrograms (mcg). During the 12-week double-blind period, participants take two (2) inhalations four times a day (QID) at approximately 7:00 AM, 12:00 PM, 5:00 PM, and bedtime for a total dose of 720 micrograms per day for those paricipants randomized to the Albuterol treatment arm. The double-blind period is followed by a 40-week open-label period in which all study participants will take Albuterol Spiromax 90 micrograms (mcg)/inhalation as needed (PRN).<br>* Other names: ProAir® RespiClick, Albuterol multi-dose dry powder inhaler (MDPI);|
| Placebo Comparator: Placebo Spiromax<br>Placebo delivered using a multi-dose dry powder inhaler (Spiromax) as 2 inhalations four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they administer albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN). | Drug: Placebo Spiromax<br>* Placebo as a dry-powder inhaled orally using the Spiromax inhaler. During the 12-week double-blind period, participants take two (2) inhalations four times a day (QID) at approximately 7:00 AM, 12:00 PM, 5:00 PM, and bedtime.<br>Drug: Albuterol Spiromax<br>* Albuterol as a dry-powder inhaled orally using the Spiromax inhaler. Each inhalation delivers 90 micrograms (mcg). During the 12-week double-blind period, participants take two (2) inhalations four times a day (QID) at approximately 7:00 AM, 12:00 PM, 5:00 PM, and bedtime for a total dose of 720 micrograms per day for those paricipants randomized to the Albuterol treatment arm. The double-blind period is followed by a 40-week open-label period in which all study participants will take Albuterol Spiromax 90 micrograms (mcg)/inhalation as needed (PRN).<br>* Other names: ProAir® RespiClick, Albuterol multi-dose dry powder inhaler (MDPI);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. 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 49 (study termination) | 
| Changes From Screening in the Results of the Physical Examination That Are Clinically Significant in the Opinion of the Investigator | A complete physical examination was planned at study screening, week 12 and week 52 or early termination/discontinuation of the participant. At weeks 12 and 52,the qualified healthcare professional was to evaluate whether each physical finding is a new finding, worsening, improvement or resolution of an existing condition compared with the baseline physical exam. Where possible, the same qualified healthcare professional that performed the physical examination at study screening should perform all the scheduled physical examinations. | Days -15 to -8 (Screening), Week 12, Week 52 | 
| Changes From Screening in the Results of the Laboratory Evaluations That Are Clinically Significant in the Opinion of the Investigator | Blood samples were to collected for laboratory evaluations at the screening visit and at weeks 12 and 52 or early termination/discontinuation of the participant. The blood samples were to be drawn after an overnight fast of at least 6 hours and analyzed by a central laboratory. | Days -15 to -8 (Screening), Week 12, Week 52 | 
| Changes From Screening in the Results of the Electrocardiograms (ECGs) That Are Clinically Significant in the Opinion of the Investigator | A standard 12-lead ECG was to be performed at screening and at week 12 and week 52 (TV15) or early termination/discontinuation of the participant. The ECG recording methods were to be centralized and standardized across all study subjects. | Days -15 to -8 (Screening), Week 12, Week 52 | 
| Changes From Screening in the Vital Signs That Are Clinically Significant in the Opinion of the Investigator | Vital sign measurements (heart rate and blood pressure) were to be evaluated as part of the safety profile assessment. The participant was to be seated at least 2 minutes before vital signs were performed. Either an electronic or manual sphygmomanometer could be used. | Days -15 to -8 (Screening), Week 12, Week 52 | 

 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