Clinical trial NCT01662778
Conditions: Asthma
Keywords: Monodisperse aerosols Asthmatics Pharmacokinetics AMP Challenge Multiple Breath Nitrogen Washout
Sponsor: Imperial College London
Start date: 2011-12-01; Completion date: 2012-12-01
Enrollment: 21 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The objective here is to determine that the efficiency of inhaled drug delivery can be improved by using a fine mist cloud of drug particles (as opposed to a coarse mist cloud of drug particles). This information will be valuable in designing new inhalers in order to improve their beneficial effects and reduce their side effects, by using the least possible drug dose to achieve a good patient response.

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Detailed description:
Inhaled drug therapy is an established and effective means to treat lung diseases such as asthma. Medical inhalers ('puffers') form the cornerstone of the management of patients with respiratory/lung problems. Inhaled treatment usually comprises placing an inhaler (puffer) in the mouth and inhaling a measured dose of drug from the puffer. The drug dose needs to bypass the throat and reach the lungs, in order to be effective.

However, there is still much that is not known about what actually happens to the inhaled drug in the lungs. Much of the inhaled drug dose from a puffer fails to reach the lungs with most of it hitting the back of the throat. Only a small amount (approximately as little as 20%) of the drug reaches the important parts of the lungs to have a beneficial effect. Particle size has a significant influence on our ability to get the inhaled drug to the important parts of the lungs. In order to get the inhaled drug to these important parts of the lungs it is necessary to understand how much of a clinical improvement is obtained when identical doses of FP are inhaled with different particle sizes.

Inhalers (are a bit like hairspray cans or air fresher cans) and produce aerosol clouds of particles. Medical inhalers come in different shapes and sizes and have a variety of drugs used to treat patients. Inhalers used in routine clinical practice produce a 'coarse' mist of drug particles, which have the potential for side effects, as different sized particle will deposit in different parts of the respiratory tract and include; the mouth, the throat, the windpipe, and the bloodstream (all places we do not want the inhaled drug to 'deposit') and the lungs (where we do want the drug to go). This is particularly an important consideration with inhaled steroids that are commonly used in the management of patients with asthma and bronchitis and emphysema. For example, a common side effect is that the deposition of steroid drug in the throat can lead to a hoarse or altered voice, and sometimes thrush of the throat.

In contrast, monodisperse aerosols are special 'fine-mist' aerosols, where all the drug particles are of one particle size. We can use these aerosols to investigate the science of the way the lungs handle and respond to inhaled drugs of different particle size.

We shall use small and large drug particles. In order to deliver the inhaled drug as a monodisperse aerosol, we shall use a spinning top aerosol generator (STAG) (a large research nebuliser machine) which is able to selectively generate aerosol clouds that have a fine mist. This is an efficient machine compared to current nebulisers used in routine clinical practice, where it can often be difficult to control the inhaled drug dose to the patient; sometimes the patient gets too little a dose because the nebuliser is an inefficient inhaler device. But, also, by improving the efficiency of inhaled drug delivery - will allow lower drug doses to be used - which will decrease the potential for patient side effects.

We have previously undertaken and published in the medical literature a series of clinical studies in patients with asthma using the STAG 'fine-mist' aerosol system and the 'reliever' drug salbutamol (ventolin). Also, we are currently undertaking the investigation of the pharmacokinetic effects of inhaling the 'preventer ' steroid class of drug FP at different particle sizes.

The main question is now can we improve the beneficial effect the inhaled drug has on the lungs by altering the particle size. This study will form the next step in the investigation of this commonly used inhaled steroid Fluticasone Propionate, used in asthma, bronchitis and emphysema patients.

We hope this investigation will help to provide further answers to the rationale that by improving the efficiency of drug delivery (by changing drug particle size) one may improve inhaled drug delivery and improve clinical benefit.

Arms: arm 1: 50 mg of monodisperse Fluticasone Propionate delivered as 1.5 microns aerosol followed by AMP PC20 challenge test arm 2: 50 mg of monodisperse Fluticasone Propionate delivered as 6.0 microns aerosol followed by AMP PC20 challenge test arm 3: No active drug, just solvent delivered from STAG followed by AMP PC20 challenge test arm 4: Fluticasone Propionate , Metered dose inhaler, 250 mg dose followed by AMP PC20 challenge test
Interventions: intervention 1: 1.5 microns at 50mg intervention 2: 6 microns at 50mg intervention 3: Placebo Comparator intervention 4: MDI FP
Intervention descriptions: intervention 1: STAG generated monodisperse 1.5micron particles intervention 2: STAG generated monodisperse 6 micron particles intervention 3: No drug just solvent intervention 4: None

Protocol documents: