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