IPF Drug Deposition Study

Idiopathic Pulmonary Fibrosis Clinical Trial

— TOPICAL-IPF  

Official title:

A Study of the Pharmacokinetics and Deposition of Inhaled Salbutamol in Patients With Idiopathic Pulmonary Fibrosis (TOPICAL-IPF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01457261
• Other study ID #: RBHIPF02
• Secondary ID: 2011-000336-29
• Status: Completed
• Phase: Phase 1
• First received: October 19, 2011
• Last updated: November 4, 2014
• Start date: April 2012
• Est. completion date: November 2014

Study information

• Verified date: November 2014
• Source: Royal Brompton & Harefield NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healtcare products Regulatory Agency (MHRA)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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 ß2 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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• Salbutamol
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.

Locations

Country	Name	City	State
United Kingdom	Royal Brompton Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
Royal Brompton & Harefield NHS Foundation Trust	GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

Maher TM, Wells AU, Laurent GJ. Idiopathic pulmonary fibrosis: multiple causes and multiple mechanisms? Eur Respir J. 2007 Nov;30(5):835-9. Review. — View Citation

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. Epub 2005 Sep 28. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Serum salbutamol change	Pharmacokinetics of inhaled drug absorbtion	0 - 6 hours	No
Secondary	Urinary salbutamol concentration	Measurement of pharmacokinetics of salbutamol absorbtion through measurement of urinary excretion	0-8 hours	No
Secondary	Penetration index	Measure of pattern of drug distribution (procximal versus distal lung) as determined by lung scintigraphy	5 minutes post administration	No