IPF Drug Deposition Study

NCT01457261 | Completed Phase 1

• 2 other identifiers: RBHIPF022011-000336-29
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Idiopathic pulmonary fibrosis is a relentlessly progressive disease that is responsible for the deaths of over 5000 people in the UK each year. At present, despite a dramatic increase in clinical trials in the last decade, there are no licensed treatments for IPF. The pathogenesis of the condition remains incompletely understood, nonetheless there is good evidence to suggests that the condition arises as the consequence of an aberrant wound healing response in genetically susceptible individuals. Basic science research into IPF has identified a wide range of potential treatment targets. However, in many cases developing compounds to act against these targets, because of their role in normal wound healing, is limited by the possibility of major systemic side effects. The lung is highly amenable to topical therapy in the form of inhaled drug preparations and this route is utilised in the treatment of the majority of respiratory disease. The inhaled route offers a number of important potential advantages for administration of therapy to patients with IPF. Firstly, by limiting systemic exposure to drugs, the inhaled route offers the potential for achieving higher lung doses of drugs that might otherwise cause systemic toxicity. Secondly, inhaled treatment may more effectively reach the areas of abnormality in IPF, namely the hyperplastic epithelium and the underlying fibroblastic foci. Thirdly, the inhaled route offers an alternative to parenteral administration of compounds that are poorly absorbed through the gastro-intestinal tract e.g. monoclonal antibodies. It should be noted however, that the fibrosis in IPF develops peripherally involving the alveolar interstitium and the terminal bronchioles. Furthermore, the disease causes architectural destruction and distortion of the lung that is liable to alter the normal laminar flow of air (and inhaled particles) through the bronchial tree. It is therefore, by no means certain that it is possible to deliver inhaled therapies directly to regions of fibrosis in IPF. The feasibility of delivering inhaled drugs in IPF has not been previously studied. This research by assessing the effect of particle size on inhaled particle deposition and by relating to this the pharmacokinetic profile of salbutamol aims to validate the potential of the inhaled route in IPF. This study is an important precursor to the development of specific topical therapies for patients with IPF.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

interstitial lung disease; drug deposition; lung imaging; respiratory

Outcome Measures

Primary Outcomes (1)

• Total lung deposition

  Effect of particle size and delivery device will be assessed by measuring total lung deposition of radio-labelled particles on scintegraphic images

  5 minutes post administation

Secondary Outcomes (3)

• Serum salbutamol change

  0 - 6 hours

• Urinary salbutamol concentration

  0-8 hours

• Penetration index

  5 minutes post administration

Study Arms (4)

Partical size 1

EXPERIMENTAL

Monodisperse particle delivered with radiolabel

Drug: Salbutamol

Particle size 2

EXPERIMENTAL

Monodisperse particle delivered with radiolabel

Drug: Salbutamol

Nebulised salbutamol

EXPERIMENTAL

Polydisperse particle via a nebuliser

Drug: Salbutamol

Salbutamol MDI

EXPERIMENTAL

Unlabelled salbutamol via a metered dose inhaler

Drug: Salbutamol

Interventions

Salbutamol DRUG

Radiolabelled salbutamol to be administered as a monodisperse particle via a spinning top aerosol generator or else as a polydisperse mist via a nebuliser or metered dose inhaler.

Also known as: Ventolin

Nebulised salbutamol; Partical size 1; Particle size 2; Salbutamol MDI

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosis of definite or probable idiopathic pulmonary fibrosis as defined by the ATS/ERS consensus criteria

You may not qualify if:

• co-existent respiratory disease
• use of B2 agonists in preceding two weeks
• DLco and/or FVC falling outside the criteria for either mild or severe IPF.
• Ongoing involvement in clinical trials assessing novel IPF therapies.
• Previous adverse reaction to short or long acting β2 agonist.
• Pregnancy or active breast feeding
• Any contraindication to taking inhaled beta-2 adrenoceptor agonists (especially salbutamol) as listed in the British National Formulary will not be entered into this study.
• an acute respiratory exacerbation requiring emergency room treatment and/ or hospitalisation within four weeks of visit 1 (screening visit)

Sponsors & Collaborators

• Royal Brompton & Harefield NHS Foundation Trust: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Royal Brompton Hospital

London, London, SW3 6NP, United Kingdom

Location

Related Publications (4)

• Maher TM, Wells AU, Laurent GJ. Idiopathic pulmonary fibrosis: multiple causes and multiple mechanisms? Eur Respir J. 2007 Nov;30(5):835-9. doi: 10.1183/09031936.00069307.

  PMID: 17978154 BACKGROUND

• Usmani OS, Biddiscombe MF, Underwood SR, Barnes PJ. Characterization of the generation of radiolabeled monodisperse albuterol particles using the spinning-top aerosol generator. J Nucl Med. 2004 Jan;45(1):69-73.

  PMID: 14734675 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, Yang S, Meah S, Oballa E, Simpson JK, Fahy WA, Marshall RP, Lukey PT, Maher TM. The topical study of inhaled drug (salbutamol) delivery in idiopathic pulmonary fibrosis. Respir Res. 2018 Feb 6;19(1):25. doi: 10.1186/s12931-018-0732-0.

  PMID: 29409488 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial

Interventions

Albuterol

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Study Officials

• Toby M Maher, MB PhD

  Royal Brompton & Harefield NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2011
• First Posted: October 21, 2011
• Study Start: April 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: November 5, 2014

Record last verified: 2014-11

Locations

GB (1)