Long Term Safety Study of Levalbuterol and Racemic Albuterol in Subjects Twelve Years of Age and Older With Asthma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of levalbuterol as compared to racemic albuterol based on the frequencies of adverse events reporting during a 12-month period of chronic dosing of adolescent and adult subjects with asthma.

Detailed Description
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This was a randomized, open-label, active controlled, multicenter, parallel-group safety study in subjects 12 years of age and older with asthma. Subjects of appropriate age who completed the Phase III levalbuterol HFA MDI trials (Studies 051-353 or 051-355) were eligible to participate. Studies 051-353 and 051-355, both entitled An Efficacy and Safety Study of Levalbuterol, Racemic Albuterol and Placebo in Subjects Twelve Years of Age and Older with Asthma were multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group studies of up to nine weeks in duration (a one-week single-blind placebo run in period followed by an eight-week double-blind treatment period). Subjects who completed Studies 051 353 and 051 355 but who were not immediately eligible to rollover into the current study could also participate but only after a 30-day washout. New subjects and subjects who participated in the Phase III trials who were not immediately eligible (ie, had a >30-day washout) were considered to be de novo subjects.Study participation included 10 study visits over a 12 month period. This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.

Official Title
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Long Term Safety Study of Levalbuterol and Racemic Albuterol in Subjects Twelve Years of Age and Older With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: levalbuterol tartrate HFA MDI
* Drug: racemic albuterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Willing and able to comply with study procedures and visit schedules Females 12-60 yrs must have a negative serum pregnancy test at study start Women of child bearing potential must use acceptable method of birth control throughout study Confirmed diagnosis of asthma minimum of 6 mos. prior to study start Have stable baseline asthma and have been using B-adrenergic agonist, and/or anti-asthma anti-inflammatory meds, and/or OTC asthma meds. >6 mos. prior to study start In good health with exception of reversible airways disease and not suffering from any chronic condition that might affect their respiratory function Had chest X-ray w/in 12 mos. prior to randomization that is not diagnostic of pneumonia, atelectasis, pulmonary fibrotic disease, pneumothorax, chronic obstructive pulmonary disease etc. Subject rolling over from either Sepracor study 051-353 or 051-355 must have successfully completed the study Subject who is not immediately rolled over from Sepracor study 051-353 or 051-355 must wait >30 days and will be regarded as a de novo subject Able to complete daily diary cards and medical event calendars reliably, understand dosing instructions, demonstrate how to use the MiniWright PEF meter. Minor subjects must have a parent/legal guardian assist them during the study with these activities Exclusion Criteria Female who is pregnant or lactating Participated in investigational drug study w/in 30 days prior to study start, or currently participating in another clinical trial, other than Sepracor studies 051-353 or 051-355 Subject who early terminated from Sepracor study 051-353 or 051-355 Subject whose schedule prevents him or her from taking the first daily dose of study medication and/or starting study visits before 10 AM Have travel commitments during the study that would interfere with trial measurements and/or compliance History of hospitalization for asthma w/in 45 days prior to study start, or scheduled for in-patient hospitalization, including elective surgery during the trial Subject with a known sensitivity to levalbuterol or racemic albuterol, or any of the excipients contained in any of these formulations Subject using any prescription drug with which albuterol sulfate is contraindicated Subject with currently diagnosed life-threatening asthma History of cancer (exception: basal cell carcinoma in remission) Subject with hyperthyroidism, diabetes, hypertension, cardiac diseases or seizure disorders that currently are not well controlled by medication or may interfere with the successful completion of this protocol History of substance abuse or drug abuse within 12 months preceding V1 Subject with >10 pack/yr history of cigarette smoking or use of any tobacco products within 6 months of study start Documented history of bronchopulmonary aspergillosis or any form of allergic alveolitis Have suffered from a clinically significant upper or lower respiratory tract infection in the 2 weeks prior to study start Subject who is a staff member or relative of a staff member

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>levalbuterol 90 mcg MDI QID | Drug: levalbuterol tartrate HFA MDI<br>* levalbuterol MDI 90 mcg QID<br>* Other names: Xopenex HFA MDI;|
| Active Comparator: 2<br>racemic albuterol HFA MDI 180 mcg QID | Drug: racemic albuterol<br>* racemic albuterol HFA MDI 180 mcg QID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of post-randomization adverse events |  | Weeks -1, 0, 1, 2, 3, 10, 11, 18, 19, 22, 23, 26, 27, 30, 31, 34, 35, 38, 39, 43, 44, 47, 48, 52, 53 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of discontinuations due to adverse events |  | Weeks -1, 0, 1, 2, 3, 10, 11, 18, 19, 22, 23, 26, 27, 30, 31, 34, 35, 38, 39, 43, 44, 47, 48, 52, 53 | 
| time-to-selected adverse events (AEs with an incidence ≥5%) |  | Weeks -1, 0, 1, 2, 3, 10, 11, 18, 19, 22, 23, 26, 27, 30, 31, 34, 35, 38, 39, 43, 44, 47, 48, 52, 53 | 
| asthma attacks, asthma adverse events, and expanded-definition asthma events |  | Weeks -1, 0, 1, 2, 3, 10, 11, 18, 19, 22, 23, 26, 27, 30, 31, 34, 35, 38, 39, 43, 44, 47, 48, 52, 53 | 
| clinical laboratory values |  | Weeks -1, 0, 10, 11, 26, 27, 43, 44, 52, 53 | 
| vital signs (blood pressure, heart rate, respiration rate, and body temperature) |  | Weeks -1, 0, 1, 2, 3, 10, 11, 18, 19, 26, 27, 34, 35, 43, 44, 52, 53 | 
| ECG parameters |  | Weeks -1, 0, 1, 10, 11, 26, 27, 43, 44, 52, 53 | 
| physical examinations |  | Weeks -1, 0, 26, 27, 52, 53 | 
| rescue medication, and daytime asthma control days |  | Weeks -1, 0, 1, 2, 3, 10, 11, 18, 19, 22, 23, 26, 27, 30, 31, 34, 35, 38, 39, 43, 44, 47, 48, 52, 53 | 
| FEV1, FVC, FEF25-75%, peak expiratory flow |  | Weeks -1, 0, 1, 2, 3, 10, 11, 18, 19, 26, 27, 34, 35, 43, 44, 52, 53 | 
| Asthma Quality of Life Questionnaire (AQLQ) |  | Weeks 0, 26, 27, 52, 53 | 
| subject and physician global evaluations |  | Weeks 26, 27, 52, 53 | 
| (S) and (R) albuterol plasma concentrations |  | Weeks -1, 0, 10, 11, 26, 27, 43, 44, 52, 53 | 
| subject assessment of study inhaler device performance |  | Weeks -1, 0, 1, 2, 3, 10, 11, 18, 19, 22, 23, 26, 27, 30, 31, 34, 35, 38, 39, 43, 44, 47, 48, 52, 53 |