Pharmacokinetics of Inhaled Monodisperse Fluticasone Propionate

NCT00692978 | Completed Phase 4 Results

• 1 other identifier: 08/H0712/63
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Healthy; Asthma

Keywords

Monodisperse aerosols; Healthy Volunteers; Asthmatics; Pharmacokinetics; Randomized

Outcome Measures

Primary Outcomes (1)

• AUC Fluticasone Propionate (FP)

  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 0 and 12 hours.

  12 hours

Study Arms (2)

Asthma

EXPERIMENTAL

Asthma patients

Drug: Fluticasone Propionate_1.5; Drug: Fluticasone Propionate_3; Drug: Fluticasone Propionate_6; Drug: FP From Active 250 ug MDI Inhaler

Healthy volunters

ACTIVE COMPARATOR

Healthy participants

Drug: Fluticasone Propionate_1.5; Drug: Fluticasone Propionate_3; Drug: Fluticasone Propionate_6; Drug: FP From Active 250 ug MDI Inhaler

Interventions

Fluticasone Propionate_1.5 DRUG

Dose 50 micrograms (total dose), Monodisperse aerosol with particle size of drug 1.5 micros, inhaled

Asthma; Healthy volunters

Fluticasone Propionate_3 DRUG

Dose 50 micrograms (total dose), Monodisperse aerosol with particle size of drug 3.0 microns, inhaled

Asthma; Healthy volunters

Fluticasone Propionate_6 DRUG

Dose 50 micrograms (total dose), Monodisperse aerosol with particle size of drug 6.0 microns, inhaled

Asthma; Healthy volunters

FP From Active 250 ug MDI Inhaler DRUG

Monodisperse aerosols inhaled of Fluticasone Propionate at 250micrograms dose with active MDI inhaler

Asthma; Healthy volunters

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Volunteers
• Healthy non smoking participants
• Male or female aged above 18 years
• No history of respiratory disease
• 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.
• No history of allergic disease i.e., a negative skin prick test
• Participants who are free from significant cardiac, gastrointestinal, hepatic, renal, hematological, neurological and psychiatric disease.
• 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
• Male or females aged greater than 18 years with a documented history of reversible airways disease responding to beta2-adrenergic therapy.
• Asthmatic patients who are free from significant cardiac, gastrointestinal, hepatic, renal, hematological, neurological and psychiatric disease.
• Patients who are stabilized on 500 micrograms or less of inhaled beclomethasone dipropionate or alternative inhaled corticosteroid (budesonide or ciclesonide).
• Patients who are able and willing to give written informed consent to take part in the study
• 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.

You may not qualify if:

• Healthy Volunteers and Asthmatics
• 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
• Those requiring greater than 500 micrograms of inhaled beclomethasone dipropionate or alternative inhaled corticosteroid (budesonide or ciclesonide).
• Subjects that have received inhaled or intravenous fluticasone propionate in the last 2 months.
• Those whose reversible airways obstruction has been unstable in the last four weeks (indicated by any change in their maintenance therapy).
• Those participants who have had a lower respiratory tract infection in the previous four weeks
• Those who have donated 450ml blood or more within the previous 1 month.
• Those who have a history of drug allergy which, in the opinion of the Unit Physician, contraindicates his/her participation in the study.
• 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.
• 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).
• 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
• Those who have experienced an acute asthma exacerbation requiring emergency room treatment and/or hospitalization within one month of visit 1.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (2)

Asthma Lab, Royal Brompton Hospital

London, United Kingdom

Location

Department of Nuclear Medicine, Royal Brompton Hospital

London, United Kingdom

Location

Related Publications (4)

• Biddiscombe MF, Barnes PJ, Usmani OS. Generating monodisperse pharmacological aerosols using the spinning-top aerosol generator. J Aerosol Med. 2006 Fall;19(3):245-53. doi: 10.1089/jam.2006.19.245.

  PMID: 17034300 BACKGROUND

• Usmani OS, Biddiscombe MF, Barnes PJ. Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size. Am J Respir Crit Care Med. 2005 Dec 15;172(12):1497-504. doi: 10.1164/rccm.200410-1414OC. Epub 2005 Sep 28.

  PMID: 16192448 BACKGROUND

• Usmani OS, Biddiscombe MF, Nightingale JA, Underwood SR, Barnes PJ. Effects of bronchodilator particle size in asthmatic patients using monodisperse aerosols. J Appl Physiol (1985). 2003 Nov;95(5):2106-12. doi: 10.1152/japplphysiol.00525.2003. Epub 2003 Aug 1.

  PMID: 12897033 BACKGROUND

• Biddiscombe MF, Usmani OS, Barnes PJ. A system for the production and delivery of monodisperse salbutamol aerosols to the lungs. Int J Pharm. 2003 Mar 26;254(2):243-53. doi: 10.1016/s0378-5173(03)00032-2.

  PMID: 12623200 BACKGROUND

MeSH Terms

Conditions

Asthma

Interventions

Metered Dose Inhalers

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nebulizers and Vaporizers; Equipment and Supplies

Results Point of Contact

• Title: Dr Omar Usmani
• Organization: Imperial College London

o.usmani@imperial.ac.uk

02073158051

Study Officials

• O S Usmani, MD, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two groups (asthma and healthy) go through different particle size of monodisperse aerosol treatments

Study Record Dates

• First Submitted: June 4, 2008
• First Posted: June 6, 2008
• Study Start: August 1, 2008
• Primary Completion: July 3, 2011
• Study Completion: July 3, 2011
• Last Updated: November 25, 2020
• Results First Posted: November 25, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)