Onset of Action of Advair Hydrofluoroalkane (HFA) 115/21 in Comparison to Symbicort Pressurised Metered-Dose Inhalers (pMDI) 160/4.5 Measured by Impulse Oscillometry (IOS)

Study Overview
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Brief Summary
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The objectives of this study are to measure Impulse Oscillometry (IOS) in patients with asthma extensively at baseline in patients with mild-to-moderate asthma, treated with as-needed short acting beta agonist only, to measure respiratory resistance and small airway dysfunction accurately and precisely at baseline, from which to measure onset of action of Advair MDI in comparison with that of Symbicort MDI. Initial screening will assess IOS resistance and small airway dysfunction and its response to short acting beta agonist (SABA). Patients will be selected from among those who manifest a 40% improvement in small airway function assessed by IOS low frequency reactance after SABA compared to baseline. After screening, patients will be randomized to receive either Advair or Symbicort; and will be assessed at randomization before and at several intervals after initial dosing, up to 4 hours. Patients will return again 4 weeks after randomization for extended IOS (and spirometry) testing as done at randomization.

Detailed Description
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Eligibility criteria include age 12-45 years, with current treatment of asthma with as-needed SABA only; and manifesting an acute response to SABA at screening of 40% or greater improvement in IOS low frequency reactance. After inclusion in the protocol, all subjects will receive active treatment, either with Advair or with Symbicort. Outcome measures will include large and small airway resistance and integrated low-frequency reactance calculated directly from IOS measures, and in addition, Large Airway Resistance, Small Airway Resistance and Small Airway Compliance derived from an electrical equivalent respiratory system model. Analysis of IOS data will be done post-testing by a respiratory physiologist, experienced with use of IOS and its analysis and interpretation, blinded to which treatment each individual received. Electrical-equivalent respiratory system model analyses will be done by a biomedical engineer, blinded to which treatment each individual received.

Official Title
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Onset of Action of Advair HFA 115/21 in Comparison to Symbicort pMDI 160/4.5 Measured by Impulse Oscillometry, IOS.

Conditions
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Asthma

Intervention / Treatment
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* Drug: Advair HFA MDI 115/21
* Drug: Symbicort 160/4.5 pMDI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of asthma Asthma symptoms controlled by short-acting beta agonist as-needed Age 12-45 years Exclusion Criteria: Severe asthma use of oral or inhaled corticosteroids within 30 days of screening

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Advair 115/21 MDI<br>Advair HFA 115/21 MDI Intervention = initiate intervention after screening | Drug: Advair HFA MDI 115/21<br>* Two puffs from MDI twice daily for 4 weeks<br>* Other names: Advair = fluticasone proprionate plus salmeterol;|
| Active Comparator: 2 = Symbicort 160/4.5<br>Symbicort initiated after screening | Drug: Symbicort 160/4.5 pMDI<br>* Symbicort 160/4.5 pMDI Two puffs from MDI twice daily for 4 weeks<br>* Other names: Symbicort = budesonide plus formoterol fumarate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Integrated low frequency reactance improvement after initial dosing |  | 5, 20, 40, 60, 120, and 240 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency-dependence of Resistance (R5-R20) after initial dosing |  | 5, 20, 40, 60, 120, and 240 min | 
| Model-derived estimates of Large and Small Airway Resistance and Compliance, and their changes after initial dosing |  | 5, 20, 40, 60, 120, and 240 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Forced Oscillation, Impulse Oscillometry, Electrical-equivalent respiratory system model