IPF Drug Deposition Study (TOPICAL-IPF)

November 4, 2014 updated by: Royal Brompton & Harefield NHS Foundation Trust

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, SW3 6NP
        • Royal Brompton Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

38 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Partical size 1
Monodisperse particle delivered with radiolabel
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.
Other Names:
  • Ventolin
Experimental: Particle size 2
Monodisperse particle delivered with radiolabel
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.
Other Names:
  • Ventolin
Experimental: Nebulised salbutamol
Polydisperse particle via a nebuliser
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.
Other Names:
  • Ventolin
Experimental: Salbutamol MDI
Unlabelled salbutamol via a metered dose inhaler
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.
Other Names:
  • Ventolin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total lung deposition
Time Frame: 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
5 minutes post administation

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Royal Brompton & Harefield NHS Foundation Trust

Collaborators

GlaxoSmithKline

Investigators

  • Principal Investigator: Toby M Maher, MB PhD, Royal Brompton & Harefield NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Actual)

November 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

October 19, 2011

First Submitted That Met QC Criteria

October 19, 2011

First Posted (Estimate)

October 21, 2011

Study Record Updates

Last Update Posted (Estimate)

November 5, 2014

Last Update Submitted That Met QC Criteria

November 4, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RBHIPF02
  • 2011-000336-29 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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