Efficacy and Safety Comparison of Albuterol Spiromax® and ProAir® Hydrofluoroalkane (HFA) in Pediatric Patients

A Single-Dose, Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Five-Period Crossover, Dose-Ranging Efficacy and Safety Comparison of Albuterol Spiromax® and ProAir® HFA in Pediatric Patients With Persistent Asthma

This is a multicenter, randomized, double-blind, double-dummy, placebo-controlled, single-dose, 5-treatment, 5-period, 5-way crossover study in pediatric patients with persistent asthma. The primary purpose of this study is to compare the efficacy and safety of Albuterol Spiromax with that of ProAir HFA in pediatric asthma patients at 2 delivered dose levels equivalent to 90 mcg and 180 mcg of albuterol base.

The study consists of a screening visit (SV) followed by up to 16 days by a treatment period comprising 5 visits (TV1-TV5). The treatment period visits will each be separated by a washout period lasting 2-7 days. During each treatment period visit, the forced expiratory volume in 1 second (FEV1) will be determined at 30 minutes and again immediately prior to the commencement of study medication administration, and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes after completion of study medication administration.

Inclusion Criteria:

1. Written informed consent/assent signed and dated by the patient and/or parent/caregiver/legal guardian (as appropriate) before conducting any study related procedure

2. Male or pre-menarchal female 4-11 years of age, inclusive, as of the screening visit

3. Has a documented physician diagnosis of persistent asthma of a minimum of 6 months duration that has been stable for at least 4 weeks prior to the screening visit. The asthma diagnosis must be in accordance with the National Asthma Education and Prevention Program Guidelines Expert Panel Report 3 (EPR3)

4. Has the ability to self-perform spirometry reproducibly per American Thoracic Society (ATS) guidelines

5. Has forced expiratory volume in 1 second (FEV1) 60-90% predicted for age, height, and gender at the screening visit based on the pediatric population standards as per protocol.

   Notes: (1) Predicted values of 59.50-59.99% may be rounded up to 60% and 90.01-90.49% rounded down to 90%. (2) Patients who at the screening visit fail to meet the predicted spirometry values for study entry may be allowed a single attempt to re-qualify on another day, but they must re-qualify no later than 16 days following the first attempt.

6. Demonstrates reversible bronchoconstriction as verified by a 15% or greater increase in baseline FEV1 within 30 minutes following inhalation of 180 mcg of albuterol to 200 mcg of fluticasone propionate per day or equivalent), leukotriene modifiers (LTM), inhaled cromones, or on β2-agonists alone as needed. The Inhaled corticosteroid (ICS), LTM, and cromone doses must have been stable for at least 4 weeks prior to the screening visit and are expected to be maintained for the duration of the study

7. Is maintained on low-dose inhaled corticosteroids ([ICS], less than or equal to 200 mcg of fluticasone propionate per day or equivalent), leukotriene modifiers (LTM), inhaled cromones, or on β2-agonists alone as needed. The ICS, LTM, and cromone doses must have been stable for at least 4 weeks prior to the screening visit and are expected to be maintained for the duration of the study

8. Can self-perform peak expiratory flow rate (PEF) measurements with a handheld peak flow meter

9. Has the ability to demonstrate acceptable and reproducible inhalation technique with the Spiromax and metered dose inhaler (MDI) devices

   • Other inclusion criteria apply.

Exclusion Criteria:

1. Known hypersensitivity to albuterol or any of the excipients in the inhaler formulations (lactose, ethanol, etc.)
2. Participation (receiving study medication) in any investigational drug trial within the 30 days preceding the screening visit or planned participation in another investigational drug trial at any time during this trial
3. History of severe milk protein allergy
4. History of a respiratory infection or disorder (including, but not limited to bronchitis, pneumonia, acute or chronic sinusitis, otitis media, influenza, etc.) that has not resolved within 4 weeks preceding the screening visit
5. Any asthma exacerbation requiring oral corticosteroids within 3 months of the screening visit. A patient must not have had any hospitalization for asthma within 6 months prior to the screening visit.
6. History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest, or hypoxic seizures
7. Use of any prohibited concomitant medications within the washout period prescribed per protocol prior to the screening visit.
8. Use of any medication for asthma or allergic rhinitis that is prohibited per the protocol
9. The dosage of any required intranasal corticosteroid and/or cromone has not been stable for at least 2 weeks prior to the screening visit.
10. Treated with oral or injectable corticosteroids within the 6 weeks before the screening visit.
11. Initiation of immunotherapy during the study period or dose escalation during the study period. Patients being treated with immunotherapy prior to the screening visit must be using a stable (maintenance) dose (90 days or more) to be considered for inclusion.