The Clinical Effect of Monodisperse Fluticasone Propionate in Asthma

NCT01662778 | Completed Phase 4 Results DMC

• 1 other identifier: CRO1694
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

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. .

Conditions

Asthma

Keywords

Monodisperse aerosols; Asthmatics; Pharmacokinetics; AMP Challenge; Multiple Breath Nitrogen Washout

Outcome Measures

Primary Outcomes (1)

• AMP Challenge Test PC20

  The concentration of Adenosine Monophosphate (AMP), measured in mg/ml, required to see a 20% fall in the patient's forced expiratory volume in 1 second (FEV1) is measured after taking FP aerosol. AMP is a bronchoconstrictor agent (ie it narrows the airways. We would expect that more would be necessary to produce the same 20% fall in FEV1 after receiving the FP than before due to the reduction in airways inflammation. This change is the primary outcome measure.

  2 hours

Secondary Outcomes (3)

• The Concentration of Fluticasone Propionate

  4 hours

• Spirometry

  0 and 4 hours

• Multi-breath Nitrogen Washout Test

  0 and 4 hours

Study Arms (4)

Monodisperse FP 1.5um

ACTIVE COMPARATOR

50 mg of monodisperse Fluticasone Propionate delivered as 1.5 microns aerosol followed by AMP PC20 challenge test

Drug: 1.5 microns at 50mg

Monodisperse FP 6.0um

ACTIVE COMPARATOR

50 mg of monodisperse Fluticasone Propionate delivered as 6.0 microns aerosol followed by AMP PC20 challenge test

Drug: 6 microns at 50mg

Placebo STAG

PLACEBO COMPARATOR

No active drug, just solvent delivered from STAG followed by AMP PC20 challenge test

Drug: Placebo Comparator

MDI FP

ACTIVE COMPARATOR

Fluticasone Propionate , Metered dose inhaler, 250 mg dose followed by AMP PC20 challenge test

Drug: MDI FP

Interventions

1.5 microns at 50mg DRUG

STAG generated monodisperse 1.5micron particles

Also known as: STAG 1.5um

Monodisperse FP 1.5um

6 microns at 50mg DRUG

STAG generated monodisperse 6 micron particles

Also known as: STAG 6um

Monodisperse FP 6.0um

Placebo Comparator DRUG

No drug just solvent

Also known as: STAG placebo

Placebo STAG

MDI FP DRUG

MDI FP

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, haematological, 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:

• 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 female volunteer 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 Formulary will not be entered into this study
• Those who have experienced an acute asthma exacerbation requiring emergency room treatment and/or hospitalisation within one month of visit 1.

Sponsors & Collaborators

• Imperial College London: lead
• GlaxoSmithKline: collaborator

Study Sites (2)

Asthma Lab, Royal Brompton Hospital

London, SW36LY, United Kingdom

Location

Department of Nuclear Medicine, Royal Brompton Hospital

London, SW36NP, 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

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

No limitations

Results Point of Contact

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

o.usmani@imperial.ac.uk

Study Officials

• Omar Usmani, MBBS

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 10, 2012
• Study Start: December 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: November 18, 2019
• Results First Posted: November 18, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)