IPF Drug Deposition Study (TOPICAL-IPF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Royal Brompton & Harefield NHS Foundation Trust
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Royal Brompton & Harefield NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01457261
First received: October 19, 2011
Last updated: December 31, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Idiopathic Pulmonary Fibrosis
Drug: Salbutamol
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of the Pharmacokinetics and Deposition of Inhaled Salbutamol in Patients With Idiopathic Pulmonary Fibrosis (TOPICAL-IPF)

Resource links provided by NLM:


Further study details as provided by Royal Brompton & Harefield NHS Foundation Trust:

Primary Outcome Measures:
  • Total lung deposition [ Time Frame: 5 minutes post administation ] [ Designated as safety issue: No ]
    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:
  • Serum salbutamol change [ Time Frame: 0 - 6 hours ] [ Designated as safety issue: No ]
    Pharmacokinetics of inhaled drug absorbtion

  • Urinary salbutamol concentration [ Time Frame: 0-8 hours ] [ Designated as safety issue: No ]
    Measurement of pharmacokinetics of salbutamol absorbtion through measurement of urinary excretion

  • Penetration index [ Time Frame: 5 minutes post administration ] [ Designated as safety issue: No ]
    Measure of pattern of drug distribution (procximal versus distal lung) as determined by lung scintigraphy


Estimated Enrollment: 20
Study Start Date: April 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: Ventolin

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01457261

Contacts
Contact: Toby M Maher, MB PhD 00442073528121 ext 8018 t.maher@rbht.nhs.uk

Locations
United Kingdom
Royal Brompton Hospital Recruiting
London, United Kingdom, SW3 6NP
Contact: Toby M Maher, MB PhD    00442073528121 ext 8018    t.maher@rbht.nhs.uk   
Principal Investigator: Toby M Maher, MB PhD         
Sub-Investigator: Omar Usmani, MD         
Sponsors and Collaborators
Royal Brompton & Harefield NHS Foundation Trust
GlaxoSmithKline
Investigators
Principal Investigator: Toby M Maher, MB PhD Royal Brompton Hospital
  More Information

Publications:
Responsible Party: Royal Brompton & Harefield NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01457261     History of Changes
Other Study ID Numbers: RBHIPF02, 2011-000336-29
Study First Received: October 19, 2011
Last Updated: December 31, 2012
Health Authority: United Kingdom: Medicines and Healtcare products Regulatory Agency (MHRA)

Keywords provided by Royal Brompton & Harefield NHS Foundation Trust:
interstitial lung disease
drug deposition
lung imaging
respiratory

Additional relevant MeSH terms:
Fibrosis
Idiopathic Pulmonary Fibrosis
Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Lung Diseases
Lung Diseases, Interstitial
Pathologic Processes
Respiratory Tract Diseases
Albuterol
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Respiratory System Agents
Therapeutic Uses
Tocolytic Agents

ClinicalTrials.gov processed this record on October 23, 2014