Flunisolide HFA in Children With Small Airway Disease

This is a prospective, randomized, parallel, open label study. The primary aim is to compare the average change in spirometric values (Forced expiratory volume 1 (FEV1) and Forced Expiratory Flow 25-75% (FEF 25-75%) and Impulse Oscillometry System (IOS) values (Resistance at 5 Hz (R5), Resistance at 20 Hz (R20), Area of reactance (AX), Resonant frequency (Fres)) from baseline to week 6 from participants randomized flunisolide hydrofluoroalkane (HFA) 1 inhalation BID and to flunisolide HFA 2 inhalations BID. The change in scores from baseline to six week follow up will initially be compared using paired t-tests and Chi-squared tests for trend. Repeated measurements will be analyzed using generalized linear mixed-effects regression modeling (GLMM) techniques. For continuous outcomes (e.g. FEV1, FEF 25-75%, Fres, reactance at 5 Hz (X5), AX, R5-R20). The identity link function and normal distribution will be used. For count data (e.g., use of Beta-agonists, episodes of coughing, episodes of wheezing, etc.) the log link function and the Poisson distribution will be used. If we dichotomize outcomes (e.g., a Beta-agonist was used, coughing occurred, etc.) the logit link function and Bernoulli distribution will be used.

Inclusion criteria

• Diagnosis of asthma
• Informed consent by parent or legal guardian
• 6 years to 18 years of age at screening visit
• ability to comply with medication use, study visits and study procedures as judged by the site investigator
• FEF 25-75% <65% of predicted as a marker for small airway disease

Exclusion criteria

• Acute wheezing at screening visit or at Baseline visit
• Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset in 1 week preceding screening visit or 3 weeks preceding baseline visit
• Oxygen saturation <95% at screening visit or at Baseline visit
• Clinically significant upper airway obstruction as determined by the Site Investigator (e.g. severe laryngomalacia, markedly enlarged tonsils, significant snoring, diagnosed obstructive sleep apnea.
• Severe gastroesophageal reflux, defined as persistent frequent emesis despite anti-reflux therapy
• Physical findings that would compromise the safety of the subject or the quality of the study data as determined by site investigator
• Inhaled Corticosteroids (ICS) use within 7 days of Baseline visit; systemic steroids within 30 days
• Cystic Fibrosis, Interstitial lung disease (ILD) history of severe Bronchopulmonary dysplasia (BPD) or other underling significant respiratory disease apart from asthma
• Potential subjects who are pregnant may not enroll in the study