Pharmacokinetics of Inhaled Monodisperse Fluticasone Propionate
Condition: Healthy; Asthma
Intervention: Fluticasone Propionate_1.5; Fluticasone Propionate_3; Fluticasone Propionate_6; FP From Active 250 ug MDI Inhaler
Intervention description: Dose 50 micrograms (total dose), Monodisperse aerosol with particle size of drug 1.5 micros, inhaled; Dose 50 micrograms (total dose), Monodisperse aerosol with particle size of drug 3.0 microns, inhaled; Dose 50 micrograms (total dose), Monodisperse aerosol with particle size of drug 6.0 microns, inhaled; Monodisperse aerosols inhaled of Fluticasone Propionate at 250micrograms dose with active MDI inhaler
Intervention MeSH terms: Fluticasone; Xhance
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: Two groups (asthma and healthy) go through different particle size of monodisperse aerosol treatments
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Monodisperse aerosols; Healthy Volunteers; Asthmatics; Pharmacokinetics; Randomized

Summary:

      Asthma is most effectively treated by delivering inhaled drugs from an inhaler (puffer)
      directly into the lungs. Inhaled steroids are used in asthmatic patients to dampen down lung
      inflammation, which unchecked, can often lead to patient symptoms. Inhalers deliver a mist
      containing particles of lots of different sizes (like hairsprays). Medical puffers used by
      patients produce a 'coarse' mist of drug particles, which have the potential for side
      effects, as different sized particles will reach different parts of the airways and include;
      the mouth, the throat, the windpipe, and the bloodstream (all places we do not want the
      inhaled drug to go - and can give rise to important side effects)and, the lungs (where we do
      want the drug to 'deposit').

      Our aim in this study is to test an inhaled steroid by giving it to subjects as a 'fine' mist
      containing drug particles of nearly all one size using a research nebuliser (a Spinning Top
      Aerosol Generator). We shall use small, intermediate and large drug particle mists. We aim to
      find out how much of the drug goes to the blood stream for each particle mist and compare it
      with the standard puffers used in routine clinical practice.

      We hope this study will provide information to the rationale that by improving the efficiency
      of drug delivery (by changing drug particle size) one may improve inhaled drug delivery and
      ultimately, clinical patient benefit.

      Healthy volunteers and asthmatic patients will be recruited at the Royal Brompton Hospital
      London. The study is funded by GlaxoSmithKline, Research & Development, U.K.
    

Eligibility criteria:

        Inclusion Criteria:

        Healthy Volunteers

        Participants will be included if they meet all of the following inclusion criteria

          1. Healthy non smoking participants

          2. Male or female aged above 18 years

          3. No history of respiratory disease

          4. Normal baseline spirometry as predicted for age, sex and height (we have excluded
             those with abnormal spirometry as this may indicate an underlying lung condition that
             needs attention, and such participants will be told their result and with their
             consent, the information will be forwarded to their General Practitioner, as part of
             the safety and well being of the research participant.

          5. No history of allergic disease i.e., a negative skin prick test

          6. Participants who are free from significant cardiac, gastrointestinal, hepatic, renal,
             hematological, neurological and psychiatric disease.

          7. Not taking any regular medication that is contraindicated in those about to receive
             fluticasone propionate (as indicated in the British National Formularly); other than
             the oral contraceptive pill.

        Asthmatics

          1. Male or females aged greater than 18 years with a documented history of reversible
             airways disease responding to beta2-adrenergic therapy.

          2. Asthmatic patients who are free from significant cardiac, gastrointestinal, hepatic,
             renal, hematological, neurological and psychiatric disease.

          3. Patients who are stabilized on 500 micrograms or less of inhaled beclomethasone
             dipropionate or alternative inhaled corticosteroid (budesonide or ciclesonide).

          4. Patients who are able and willing to give written informed consent to take part in the
             study

          5. Not taking any regular medication that is contraindicated in those about to receive
             fluitcasone propionate (as indicated in the British National Formularly); other than
             the oral contraceptive pill.

        Exclusion Criteria:

        Healthy Volunteers and Asthmatics

          1. Those requiring maintenance oral or parenteral corticosteroid therapy for their
             airways disease or patients who have ceased maintenance oral or parenteral
             corticosteroid therapy within the four weeks prior to visit 1

          2. Those requiring greater than 500 micrograms of inhaled beclomethasone dipropionate or
             alternative inhaled corticosteroid (budesonide or ciclesonide).

          3. Subjects that have received inhaled or intravenous fluticasone propionate in the last
             2 months.

          4. Those whose reversible airways obstruction has been unstable in the last four weeks
             (indicated by any change in their maintenance therapy).

          5. Those participants who have had a lower respiratory tract infection in the previous
             four weeks

          6. Those who have donated 450ml blood or more within the previous 1 month.

          7. Those who have a history of drug allergy which, in the opinion of the Unit Physician,
             contraindicates his/her participation in the study.

          8. Any evidence of a positive pregnancy urine test for female volunteers or females who
             are pregnant or lactating or are likely to become pregnant during the trial. Women of
             child-bearing potential may be included in the study if, in the opinion of the
             investigator, they are taking adequate contraceptive precautions.

          9. Participants with a known or suspected allergy to corticosteroids or any component of
             the formulations and/or Suspected hypersensitivity to inhaled corticosteroid (this
             will be asked directly at the screening visit).

         10. Any patient with a contraindication to taking an inhaled steroid and specifically FP,
             listed in the British National Formularly will not be entered into this study

         11. Those who have experienced an acute asthma exacerbation requiring emergency room
             treatment and/or hospitalization within one month of visit 1.