Comparative Study of Lung Bioavailability of HFA-Seretide Via Current Spacer Devices in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the effect of plastic spacers and breath actuated spacers on respirable drug delivery of combination steroid inhaler (Seretide/Advair) and whether electrostatic charge within plastic spacers has a clinically relevant impact on the inhaled steroid delivery.

Detailed Description
-----------------
Conventional plastic spacers are bulky and can be influenced by electrostatic charge, which can reduce respirable dose delivery especially when used brand new out of the box. Breath actuated integrated vortex spacer (Synchro-Breathe) is a compact palm sized antistatic device with a vortex chamber which is designed to be more patient friendly and free from the effects of electrostatic charge. The systemic bioavailability from the lung of inhaled fluticasone and salmeterol is dependent on respirable dose delivery, and hence the performance of inhaler devices can be quantified by measuring the degree of adrenal suppression and fall in serum potassium(K) as surrogates for delivered lung dose. This study attempts to compares the systemic bioavailability from the lung in real life conditions for Fluticasone/Salmeterol combination (measured in terms of relative adrenal suppression and fall in serum K) via the breath actuated Synchro-Breathe device, pMDI( Seretide Evohaler), and Aerochamber Plus & Volumatic spacer used brand new out of the box in healthy volunteers.

Official Title
-----------------
Comparative Study of Lung Bioavailability of HFA-Seretide Via Current Spacer Devices in Healthy Volunteers

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: Seretide 250(8puffs) via Evohaler actuator
* Drug: Seretide 250 (8 puffs)/placebo via Volumatic spacer
* Drug: Seretide 250/placebo 8 puffs via Aerochamber Plus spacer
* Drug: Seretide 250/placebo via Synchro-Breathe


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy Volunteers Male or female 18-65 Informed Consent Ability to comply with the requirements of the protocol Exclusion Criteria: No respiratory disease Smokers Recent respiratory tract infection (2 months). Any other clinically significant medical condition such as unstable angina, acute myocardial infarction in the preceding 3 months, recent TIA/ CVA,that may endanger the health or safety of the participant, or jeopardise the protocol. Any significant abnormal laboratory result as deemed by the investigators Pregnancy, planned pregnancy or lactation Known or suspected contra-indication to any of the IMP's Concomitant use of medicines (prescribed, over the counter or herbal) that may interfere with the trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Evohaler<br> | Drug: Seretide 250(8puffs) via Evohaler actuator<br>* 8 puffs of Seretide250/Placebo via Evohaler actuator<br>* Other names: Advair;Drug: Seretide 250 (8 puffs)/placebo via Volumatic spacer<br>* 8 puffs of Seretide 250/placebo via volumatic spacer<br>* Other names: Advair;Drug: Seretide 250/placebo 8 puffs via Aerochamber Plus spacer<br>* Seretide 250/placebo 8 puffs via Aerochamber Plus<br>* Other names: Advair;Drug: Seretide 250/placebo via Synchro-Breathe<br>* Seretide 250/placebo 8puffs via breath actuated Synchro-Breathe device<br>* Other names: Advair;|
| Experimental: Volumatic spacer<br> | Drug: Seretide 250(8puffs) via Evohaler actuator<br>* 8 puffs of Seretide250/Placebo via Evohaler actuator<br>* Other names: Advair;Drug: Seretide 250 (8 puffs)/placebo via Volumatic spacer<br>* 8 puffs of Seretide 250/placebo via volumatic spacer<br>* Other names: Advair;Drug: Seretide 250/placebo 8 puffs via Aerochamber Plus spacer<br>* Seretide 250/placebo 8 puffs via Aerochamber Plus<br>* Other names: Advair;Drug: Seretide 250/placebo via Synchro-Breathe<br>* Seretide 250/placebo 8puffs via breath actuated Synchro-Breathe device<br>* Other names: Advair;|
| Experimental: Aerochamber Plus<br> | Drug: Seretide 250(8puffs) via Evohaler actuator<br>* 8 puffs of Seretide250/Placebo via Evohaler actuator<br>* Other names: Advair;Drug: Seretide 250 (8 puffs)/placebo via Volumatic spacer<br>* 8 puffs of Seretide 250/placebo via volumatic spacer<br>* Other names: Advair;Drug: Seretide 250/placebo 8 puffs via Aerochamber Plus spacer<br>* Seretide 250/placebo 8 puffs via Aerochamber Plus<br>* Other names: Advair;Drug: Seretide 250/placebo via Synchro-Breathe<br>* Seretide 250/placebo 8puffs via breath actuated Synchro-Breathe device<br>* Other names: Advair;|
| Experimental: Synchro-Breathe<br> | Drug: Seretide 250(8puffs) via Evohaler actuator<br>* 8 puffs of Seretide250/Placebo via Evohaler actuator<br>* Other names: Advair;Drug: Seretide 250 (8 puffs)/placebo via Volumatic spacer<br>* 8 puffs of Seretide 250/placebo via volumatic spacer<br>* Other names: Advair;Drug: Seretide 250/placebo 8 puffs via Aerochamber Plus spacer<br>* Seretide 250/placebo 8 puffs via Aerochamber Plus<br>* Other names: Advair;Drug: Seretide 250/placebo via Synchro-Breathe<br>* Seretide 250/placebo 8puffs via breath actuated Synchro-Breathe device<br>* Other names: Advair;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overnight Urinary Cortisol creatinine ratio | This outcome measure evaluates the amount of cortisol being suppressed after inhaled steroid administration. This helps to assess the systemic effect of steroid inhalation and therefore the propensity for adrenal suppression which is a noted adverse effect with high dose inhaled steroids | within 24 hours after study drug inhalation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Potassium | The serum potassium is monitored 60 minutes post study drug inhalation to assess the systemic beta-2-adrenoreceptor metabolic response. Long acting beta agonists like Salmeterol exhibit dose related reduction in serum potassium. | 60 minutes post treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
lung bioavailability, asthma, seretide, Spacer