Safety Study of Albuterol Spiromax® in Subjects With Asthma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety of Albuterol Spiromax® over 52 weeks during two dosing periods: (1) a 12-week, double-blind, placebo-controlled QID dosing period followed by (2) a 40-week, open-label PRN dosing period, and to evaluate Albuterol Spiromax® device performance through the life of the device during the study.

Official Title
-----------------
A Multi-Center 52-Week Study to Assess the Safety of Albuterol Spiromax® in Subjects With Asthma

Conditions
-----------------
Asthma

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent and HIPAA signed and dated by the subject or written informed assent signed and dated both by the subject and/or parent/caregiver/legal guardian before conducting any study related procedure. Males or females with asthma ages 12 years or older at screening. Documented history of persistent asthma and current use of an MDI containing any short-acting beta-adrenergic agonist (e.g. albuterol, levalbuterol,) on average of at least once/week over the 4-weeks prior to screening. The asthma diagnosis must be consistent with the diagnosis of asthma as per the National Asthma Education and Prevention Program. If female, is currently not pregnant, breast feeding, or attempting to become pregnant (for 4 weeks before the screening visit and throughout the duration of the study), and is of Non-childbearing potential, defined as: ≥1 year post-menopausal or Surgically sterile (tubal ligation, bilateral oophorectomy, salpingectomy, or hysterectomy) or is of Childbearing potential, has a negative serum pregnancy test, and is willing to commit to using a consistent and acceptable method of birth control General good health in the opinion of the investigator as indicated by medical history, physical examination, laboratory tests (hematology, serum chemistry and urinalysis) assessed as either normal or abnormal not clinically significant (NCS) per the principal investigator, as well as a 12-lead ECG interpreted as either Normal or Abnormal NCS as determined by the central cardiologist. Subjects must also be free of any clinically significant, uncontrolled concomitant conditions other than asthma that could interfere with study conduct, influence the interpretation of study observations/results, or put the subject at increased risk during the trial. Capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the investigator, and being compliant with all study requirements (visits, record-keeping, etc). Non-smoker for at least one year prior to the screening visit and a maximum pack-year (PY) smoking history of 10 years. Able to demonstrate proper inhaler technique with study inhaler. 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 or planned participation in another investigational drug trial at any time during this trial. A known hypersensitivity to albuterol or any of the excipients in the formulations. History of severe milk protein allergy History of an upper or lower respiratory tract infection or disorder (including, but not limited to bronchitis, pneumonia, acute or chronic sinusitis, otitis media, influenza, etc) which is not resolved at least 1 week prior to the SV. History of alcohol or drug abuse within two years preceding the SV. Use of any protocol prohibited concomitant medications for asthma (any oral β2-adrenergic agonists) or any protocol prohibited concomitant non-asthma medications including treatment with β2-adrenergic receptor antagonists and non-selective β-receptor blocking agents such as β-blocking anti-hypertensive products (administered by any route), MAO inhibitors, and/or tricyclic antidepressants. (Subject's own MDI short-acting β-agonist rescue inhaler should be used until the start of the Run-In period when a study rescue inhaler is provided.) Inability or unwillingness to comply with the protocol requirements. History of life-threatening asthma [defined here as an asthma episode requiring intubation and/or associated with hypercapnea, respiratory arrest or hypoxic seizures.] Any asthma exacerbation within 3 months of the SV requiring oral or systemic corticosteroids or any hospitalization for asthma within 6 months of the SV. Note: An exacerbation of asthma is defined as any worsening of asthma requiring any treatment other than rescue albuterol or the subject's regular asthma maintenance therapy. This includes requiring the use of systemic corticosteroids and/or emergency room visit or hospitalization or a change in subject's regular asthma maintenance treatment. A subject does not need to be withdrawn from the study due to an asthma exacerbation unless hospitalization is required or unless the principal investigator believes it is in the subjects' best interest to withdraw from the study. Previous participation in an inhaled Albuterol Spiromax® (Teva) study, with the exception of the ABS-AS-306 study. Study participation by clinical investigator site employees and/or their immediate relatives. Study participation by related or non-related individuals living in the same household, i.e. only one subject per household may participate in the study. Any clinically significant endocrine, hematological, hepatic, renal, gastrointestinal, neurological, cardiac, metabolic, immunological, any non-asthmatic acute or chronic pulmonary condition (including but not limited to bronchitis, emphysema, active tuberculosis, bronchiectasis, cystic fibrosis), and malignancy other than basal cell carcinoma. Significant is defined for this protocol as any condition that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which could affect the safety analyses. Any medical or psychological condition that in the investigator's opinion should preclude enrollment.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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-Albuterol MDPI<br>During the 12-week double-blind period, participants take 2 inhalations of placebo MDPI (multi-dose dry powder inhaler), four times a day (QID) at approximately 7:00 AM, 12:00 PM, 5:00 PM, and bedtime. The double-blind period is followed by a 40-week open-label period in which all study participants take albuterol MDPI 90 micrograms/inhalation, 2 inhalations every 4-6 hours as needed (PRN) and, if applicable, 2 inhalations 15-30 minutes prior to sports/exercise. | Drug: Placebo MDPI<br>* Placebo MDPI (multi-dose dry powder inhaler) to match the active intervention.<br>* Other names: placebo;Drug: Albuterol MDPI<br>* Albuterol MDPI (multi-dose dry powder inhaler or Spiromax®) 90 mcg/inhalation.<br>* Other names: Albuterol Spiromax;|
| Experimental: Albuterol MDPI-Albuterol MDPI<br>During the 12-week double-blind period, participants take 2 inhalations of albuterol MDPI (multi-dose dry powder inhaler or Spiromax®) 90 mcg/inhalation, four times a day (QID) at approximately 7:00 AM, 12:00 PM, 5:00 PM, and bedtime for a total daily dose of 720 micrograms per day. The double-blind period is followed by a 40-week open-label period in which all study participants take albuterol MDPI 90 micrograms/inhalation, 2 inhalations every 4-6 hours as needed (PRN) and, if applicable, 2 inhalations 15-30 minutes prior to sports/exercise. | Drug: Albuterol MDPI<br>* Albuterol MDPI (multi-dose dry powder inhaler or Spiromax®) 90 mcg/inhalation.<br>* Other names: Albuterol Spiromax;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | 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 Week 12 | 
| Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | 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. | Weeks 13-52 | 
| Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | A standard 12-lead ECG was performed at screening, week 12, and week 52 or early termination/discontinuation. The ECG recording methods were centralized and standardized across all study participants. A centralized cardiologist was responsible for providing all ECG interpretations. | Weeks 0 (screening visit), 12, and 52 | 
| Change From Baseline in Blood Pressure Measurements to Week 12 and Week 52 | Participants were seated at least 2 minutes before blood pressure measurements were obtained by either an electronic or manual sphygmomanometer. Week 12 values represent change from Week 0. Week 52 values represent change from Week 12. | Week 0, Week 12 and Week 52 | 
| Change From Baseline in Pulse Measurements to Week 12 and Week 52 | Participants were seated at least 2 minutes before pulse measurements were obtained by radial pulse. Week 12 values represent change from Week 0. Week 52 values represent change from Week 12. | Week 0, Week 12 and Week 52 | 
| Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | The physical exam was performed by a qualified healthcare professional, and when possible, the same qualified healthcare professional that performed the physical examination at study screening performed all the scheduled physical examinations. Abnormalities and clinical relevance were determined by the qualified healthcare professional. HEENT = head, eyes, ears, nose, throat | Weeks 0, 12 and 52 |