Childhood Asthma
Conditions
Brief summary
The purpose of this study is to see how two doses of Flunisolide HFA (an FDA approved inhaled medication to treat asthma) affect the small airways in children with asthma.
Detailed description
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.
Interventions
DRUGFlunisolide HFA
Sponsors
Meda Pharmaceuticals
University of Louisville
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Spirometry Forced Expiratory Volume 1 (FEV1) After Flunisolide | Before and after treatment at baseline and six week followup | the most used outcome in respiratory studies |
| Impulse Oscillometry (IOS) Area of Reactance (AX) After Flunisolide Treatment | Baseline and six week followup | A composite measure of small airway dysfunction. A reduction in IOS scores indicate an improvement. |
| Spirometry Forced Expiratory Flow 25-75% (FEF 25-75%) | baseline and six week followup | Indirectly assess small airway function. |
| Impulse Oscillometry (IOS) Resistance 5 (R5) | initial visit and six week followup | Resistance of the respiratory system at 5 Hz is a measure of total airway resistance. Elevated value is indicative of respiratory dysfunction. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Flunisolide 160 mcg Per Day Patients will receive inhaled Flunisolide HFA 80 mcg twice per day for a total of 160 mcg per day over the 6 week study period
Flunisolide HFA | 10 |
| Flunisolide 320 mcg Per Day Patients will receive inhaled Flunisolide HFA 160 mcg twice per day for a total of 320 mcg per day over the 6 week study period
Flunisolide HFA | 9 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 3 |
Baseline characteristics
| Characteristic | Flunisolide 160 mcg Per Day | Total | Flunisolide 320 mcg Per Day |
|---|---|---|---|
| Age, Continuous | 10.1 years STANDARD_DEVIATION 3.8 | 10.5 years STANDARD_DEVIATION 3.2 | 11.1 years STANDARD_DEVIATION 2.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 10 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 9 Participants | 3 Participants |
| Region of Enrollment United States | 10 participants | 19 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Male | 8 Participants | 14 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 |
| other Total, other adverse events | 0 / 10 | 0 / 9 |
| serious Total, serious adverse events | 1 / 10 | 0 / 9 |
Outcome results
Primary
Impulse Oscillometry (IOS) Area of Reactance (AX) After Flunisolide Treatment
A composite measure of small airway dysfunction. A reduction in IOS scores indicate an improvement.
Time frame: Baseline and six week followup
Population: Those subjects that completed the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Flunisolide 160 mcg Per Day Pretreatment - Baseline | Impulse Oscillometry (IOS) Area of Reactance (AX) After Flunisolide Treatment | 17.4 cmH2O/L | Standard Deviation 12.3 |
| Flunisolide 320 mcg Per Day Pretreatment - Baseline | Impulse Oscillometry (IOS) Area of Reactance (AX) After Flunisolide Treatment | 13.9 cmH2O/L | Standard Deviation 16.6 |
| Flunisolide 160 mcg Per Day Posttreatment - 6 Wks | Impulse Oscillometry (IOS) Area of Reactance (AX) After Flunisolide Treatment | 18.5 cmH2O/L | Standard Deviation 9.6 |
| Flunisolide 320 mcg Per Day Posttreatment - 6 Weeks | Impulse Oscillometry (IOS) Area of Reactance (AX) After Flunisolide Treatment | 14.9 cmH2O/L | Standard Deviation 13.5 |
p-value: 0.872Mixed Models Analysis
p-value: 0.82Mixed Models Analysis
p-value: 0.582Mixed Models Analysis
Primary
Impulse Oscillometry (IOS) Resistance 5 (R5)
Resistance of the respiratory system at 5 Hz is a measure of total airway resistance. Elevated value is indicative of respiratory dysfunction.
Time frame: initial visit and six week followup
Population: Only data for subjects who completed study are presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Flunisolide 160 mcg Per Day Pretreatment - Baseline | Impulse Oscillometry (IOS) Resistance 5 (R5) | 6.5 cmH2O(L/s) | Standard Deviation 2 |
| Flunisolide 320 mcg Per Day Pretreatment - Baseline | Impulse Oscillometry (IOS) Resistance 5 (R5) | 5.8 cmH2O(L/s) | Standard Deviation 2.3 |
| Flunisolide 160 mcg Per Day Posttreatment - 6 Wks | Impulse Oscillometry (IOS) Resistance 5 (R5) | 7.0 cmH2O(L/s) | Standard Deviation 1.4 |
| Flunisolide 320 mcg Per Day Posttreatment - 6 Weeks | Impulse Oscillometry (IOS) Resistance 5 (R5) | 6.0 cmH2O(L/s) | Standard Deviation 1.8 |
p-value: 0.62Mixed Models Analysis
p-value: 0.543Mixed Models Analysis
p-value: 0.6Mixed Models Analysis
Primary
Spirometry Forced Expiratory Flow 25-75% (FEF 25-75%)
Indirectly assess small airway function.
Time frame: baseline and six week followup
Population: Those subjects that completed the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Flunisolide 160 mcg Per Day Pretreatment - Baseline | Spirometry Forced Expiratory Flow 25-75% (FEF 25-75%) | 60.3 % of predicted | Standard Deviation 20 |
| Flunisolide 320 mcg Per Day Pretreatment - Baseline | Spirometry Forced Expiratory Flow 25-75% (FEF 25-75%) | 61.5 % of predicted | Standard Deviation 13.7 |
| Flunisolide 160 mcg Per Day Posttreatment - 6 Wks | Spirometry Forced Expiratory Flow 25-75% (FEF 25-75%) | 57.7 % of predicted | Standard Deviation 12.1 |
| Flunisolide 320 mcg Per Day Posttreatment - 6 Weeks | Spirometry Forced Expiratory Flow 25-75% (FEF 25-75%) | 65.2 % of predicted | Standard Deviation 18.9 |
p-value: 0.782Mixed Models Analysis
p-value: 0.906Mixed Models Analysis
p-value: 0.102Mixed Models Analysis
Primary
Spirometry Forced Expiratory Volume 1 (FEV1) After Flunisolide
the most used outcome in respiratory studies
Time frame: Before and after treatment at baseline and six week followup
Population: Those subjects that completed the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Flunisolide 160 mcg Per Day Pretreatment - Baseline | Spirometry Forced Expiratory Volume 1 (FEV1) After Flunisolide | 80.4 % of predicted | Standard Deviation 10.8 |
| Flunisolide 320 mcg Per Day Pretreatment - Baseline | Spirometry Forced Expiratory Volume 1 (FEV1) After Flunisolide | 78.7 % of predicted | Standard Deviation 9 |
| Flunisolide 160 mcg Per Day Posttreatment - 6 Wks | Spirometry Forced Expiratory Volume 1 (FEV1) After Flunisolide | 85.0 % of predicted | Standard Deviation 10.3 |
| Flunisolide 320 mcg Per Day Posttreatment - 6 Weeks | Spirometry Forced Expiratory Volume 1 (FEV1) After Flunisolide | 77.0 % of predicted | Standard Deviation 7.6 |
p-value: 0.148Mixed Models Analysis
p-value: 0.74Mixed Models Analysis
p-value: 0.921Mixed Models Analysis