IPF Drug Deposition Study

Phase 1

Completed

• Conditions: Idiopathic Pulmonary Fibrosis
• Interventions: Drug: Salbutamol

• Registration Number: NCT01457261
• Lead Sponsor: Royal Brompton & Harefield NHS Foundation Trust

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-10-19
• Study First Submitted QC: 2011-10-19
• Study First Posted: 2011-10-21
• Study Start: 2012-04
• Status Verified: 2014-11
• Primary Completion: 2014-11
• Study Completion: 2014-11
• Last Update Submitted: 2014-11-04
• Last Update Posted: 2014-11-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nebulised salbutamol	Salbutamol	Polydisperse particle via a nebuliser
Salbutamol MDI	Salbutamol	Unlabelled salbutamol via a metered dose inhaler
Partical size 1	Salbutamol	Monodisperse particle delivered with radiolabel
Particle size 2	Salbutamol	Monodisperse particle delivered with radiolabel

Primary Outcome Measures

Name	Time	Method
Total lung deposition	5 minutes post administation	Effect of particle size and delivery device will be assessed by measuring total lung deposition of radio-labelled particles on scintegraphic images

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Royal Brompton Hospital; 🇬🇧 London, United Kingdom