A Chronic-Dose Safety and Efficacy Study of Albuterol Multi-Dose Dry Powder Inhaler in Pediatric Asthmatics

A Three-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Chronic-Dose Safety and Efficacy Study of Albuterol Multi-Dose Dry Powder Inhaler (MDPI) Relative to Placebo in Pediatric Asthmatics

The study is to evaluate the chronic-dose efficacy and the safety of Albuterol MDPI compared to placebo in pediatric participants with asthma.

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 premenarchal female 4-11 years of age, inclusive, as of the screening visit (SV)
3. Has a documented physician diagnosis of asthma per the EPR-3 Guidelines of a minimum of 6 months duration that has been stable for at least 4 weeks prior to the SV
4. Has the ability to perform spirometry reproducibly consistent with ATS guidelines and protocol-specific guidelines
5. Has FEV1 50-95% predicted for age, height and gender at the SV following a minimum 6-hour period without β2-agonist use. (Note: Predicted values of 49.50-49.99% may be rounded up to 50% and values of 95.01-95.49% may be rounded down to 95%.)
6. Demonstrated reversible bronchoconstriction as verified by a 15% or greater increase in baseline FEV1 within 30 minutes following inhalation of 180 mcg of albuterol. (Note: Reversibility values of 14.50-14.99% may be rounded up to 15%.)
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), or inhaled cromones, and/or on short-acting β2-agonists (SABA); as needed SABA alone is acceptable. The ICS, LTM, and cromone doses must have been stable for at least 4 weeks prior to the SV and should 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. Can tolerate the withdrawal of applicable medications for qualification at screening
10. Otherwise in general good health, defined as free of any concomitant conditions or treatment that could interfere with study conduct, influence the interpretation of study observations/results, or put the patient at increased risk during the trial, and with a clinically acceptable 6-month medical history, physical examination, 12-lead electrocardiogram (ECG), and vital signs
11. Parents consenting are capable of understanding the requirements, risks and benefits of study participation, and, as judged by the investigator, capable of giving informed consent and being compliant with all study requirements (eg, visits, record-keeping)
12. The patient is able to correctly use the MDPI device, either alone or with assistance by a parent/guardian.

Exclusion Criteria

1. Known hypersensitivity to albuterol or any of the excipients in the inhaler formulations (eg, lactose, ethanol)
2. Participation (receiving study medication) in any investigational drug trial within the 30 days preceding the SV 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) that has not resolved within 4 weeks preceding the SV
5. Any asthma exacerbation requiring oral corticosteroids within 3 months of the SV. A patient must not have had any hospitalization for asthma within 6 months prior to the SV.
6. Initiation of immunotherapy during the study period or dose escalation during the study period. Patients being treated with immunotherapy prior to the SV must be using a stable (maintenance) dose (90 days or more) to be considered for inclusion.
7. 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
8. Use of any prohibited concomitant medications within the washout prescribed per protocol prior to study visits
9. Use of any medication for asthma or allergic rhinitis that is prohibited per the protocol as described in the protocol
10. The dosage of any required LTM, ICS, or inhaled cromones, has not been stable for at least 4 weeks. Intranasal corticosteroid and/or cromones have not been stable for at least two weeks prior to the SV. Allowed corticosteroid, LTM, and cromone asthma and allergy medications should be continued at the same doses during the conduct of the study.
11. Presence of any non-asthmatic acute or chronic condition, including but not limited to bronchitis, emphysema, active tuberculosis, bronchiectasis, cystic fibrosis, clinically significant cardiovascular disease (including but not limited to cardiac arrhythmias and uncontrolled hypertension), clinically significant hepatic, renal, or endocrine dysfunction, stroke, uncontrolled diabetes mellitus, hyperthyroidism, convulsive disorder, and malignancy other than basal cell carcinoma. Significant is defined as any condition that, in the opinion of the investigator, would put the safety of the patient at risk through participation, or which could affect the safety or efficacy analyses
12. Any other medical or psychological condition that in the investigator's opinion should preclude study enrollment
13. Previous participation (received MDPI study medication) in an Albuterol MDPI study
14. Study participation by clinical investigator site employees and/or their immediate relatives
15. Study participation by related or non-related individuals living in the same household, ie, only one subject per household may participate in the study at the same time.
16. Require continuous treatment with β-blockers, MAO inhibitors, tricyclic antidepressants, anticholinergics, and/or systemic corticosteroids
17. Treated with oral or injectable corticosteroids within the 6 weeks prior to SV
18. Hospitalization for acute asthma exacerbation >2 times in 12 months prior to screening and/or received emergency room treatment other than nebulized albuterol or been hospitalized for asthma exacerbations within 6 months prior to SV