IPF Drug Deposition Study

Study Overview
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Brief Summary
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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.

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

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Salbutamol


Participation Criteria
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Eligibility Criteria
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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 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)

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Partical size 1<br>Monodisperse particle delivered with radiolabel | Drug: Salbutamol<br>* 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.<br>* Other names: Ventolin;|
| Experimental: Particle size 2<br>Monodisperse particle delivered with radiolabel | Drug: Salbutamol<br>* 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.<br>* Other names: Ventolin;|
| Experimental: Nebulised salbutamol<br>Polydisperse particle via a nebuliser | Drug: Salbutamol<br>* 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.<br>* Other names: Ventolin;|
| Experimental: Salbutamol MDI<br>Unlabelled salbutamol via a metered dose inhaler | Drug: Salbutamol<br>* 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.<br>* Other names: Ventolin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum salbutamol change | Pharmacokinetics of inhaled drug absorbtion | 0 - 6 hours | 
| Urinary salbutamol concentration | Measurement of pharmacokinetics of salbutamol absorbtion through measurement of urinary excretion | 0-8 hours | 
| Penetration index | Measure of pattern of drug distribution (procximal versus distal lung) as determined by lung scintigraphy | 5 minutes post administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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interstitial lung disease, drug deposition, lung imaging, respiratory