Official Title: “The Pharmacokinetics of Inhaled Fluticasone Propionate Delivered as Monodisperse Aerosols”

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 effiency 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.

Study Type: Interventional

Study Design: Basic Science, Randomized, Double Blind (Subject, Outcomes Assessor), Placebo Control, Crossover Assignment, Pharmacokinetics Study

Study Primary Completion Date: September 2009

The clinical trial is to investigate the pharmacokinetic effects (that is how much drug is in the blood) of Fluticasone Propionate (Flixotide), a commonly used steroid drug that is inhaled in patients with asthma. We will use standard clinical Flixotide Nebules that are used with clinical nebulisers (machines used in hospital and at home − to deliver drug to patients with asthma). Current clinical nebulisers deliver a 'coarse' mist of drug, which has the potential for side effects and this is an important consideration with steroids. These Flixotide nebules will be used to deliver the drug (fluticasone propionate) as monodiperse aerosol clouds (that is the drug will be delivered as a 'fine' mist cloud to patients). In order to deliver the drug as a monodisperse aerosol, the Flixotide Nebules will be used with a spinning top aerosol (a large research nebuliser machine)which is able to selectively generate aerosol clouds that have a fine mist. A fine mist cloud leads to less deposition in the throat of the patients and a greater control of the inhaled drug reaching the lungs, and fine mist drug clouds have the potential to reduce side efects. We will also compare this to the use of a standard routine clinical dose of a Flixotide metered−dose inhaler ( a 'press and breathe' inhaler) with a spacer (plastic bubble on the end of an inhaler) delivered to patients.

Intervention(s) in this Clinical Trial

• Drug: Fluticasone Propionate
  • Dose 50 micrograms (total dose), Monodisperse aerosol with diofferemt particle size of drug (1.5, 3.0, 6.0 microns), inhaled
• Drug: Fluticasone Propionate
  • Inhaled, Metered dose inhaler, 250 micrograms dose (total dose)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Monodisperse aerosols inhaled of Fluticasone Propionate 1.5microns size at 50micrograms dose with double-dummy placebo MDI inhaler
• Experimental: 2
  • Monodisperse aerosols inhaled of Fluticasone Propionate 3.0microns size at 50micrograms dose with double-dummy placebo MDI inhaler
• Experimental: 3
  • Monodisperse aerosols inhaled of Fluticasone Propionate 6 microns size at 50micrograms dose with double-dummy placebo MDI inhaler
• Experimental: 4
  • etered dose inhaler of Fluticasone Propionate 250 micrograms dose, inhaled, with double-dummy placebo monodisperse aerosol

Primary Measures

• The main outcome measure is the concentration of Fluticasone Propionate in blood following inhalation of the dose. This will be found by calculating the area under the curve of concentration versus time from 0 to 12 hours.
  • Time Frame: Hourly for 12 hours
    Safety Issue?: No

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 fluitcasone 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Imperial College London

Overall Clinical Trial Officials and Contacts

O S Usmani, MD, PhD Principal Investigator Imperial College London  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00692978

Study ID Number: 08/H0712/63

ClinicalTrials.gov Identifier: NCT00692978

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency