The Clinical Effect of Monodisperse Fluticasone Propionate in Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 4

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.

      .
    

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.
    

Intervention name(s): 1.5 microns at 50mg; 6 microns at 50mg; Placebo Comparator; MDI FP
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): STAG generated monodisperse 1.5micron particles; STAG generated monodisperse 6 micron particles; No drug just solvent
Other intervention name(s): STAG 1.5um; STAG 6um; STAG placebo
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Monodisperse aerosols; Asthmatics; Pharmacokinetics; AMP Challenge; Multiple Breath Nitrogen Washout