Imatinib effects on lung vascular dysfunction by stimulation of injury
Research type
Research Study
Full title
A Randomized, Placebo-controlled, Double-blind Study to Investigate the Effects of the Tyrosine Kinase Inhibitor Imatinib on Pulmonary Vascular Dysfunction in a Human Experimental Model of Acute Lung Injury
IRAS ID
233444
Contact name
Muna Albayaty
Contact email
Sponsor organisation
Exvastat Ltd.
Eudract number
2017-002203-10
Duration of Study in the UK
0 years, 3 months, 30 days
Research summary
This is a randomised, double-blind, placebo-controlled clinical study of the study drug IMATINIB in healthy subjects exposed to the lipopolysaccharide (LPS) challenge. (LPS refers to lipopolysaccharide, which is a complex molecule of fat and sugar).
The main purpose of the study is to investigate the effect of IMATINIB on simulated lung injury as brought about by inhalation of LPS mist. To do this, lavage (washing out of lung with saline) samples will be collected from the subjects’ lungs after the LPS challenge. The study will also investigate the relationship between pharmacokinetics (PK) and pharmacodynamics (PD) of IMATINIB. The PK evaluation refers how the study drug is absorbed (taken up by the body), metabolised (chemically broken down), distributed through the body, and excreted (removed from the body), by measuring the amount of study drug in blood samples. The PD evaluation will assess the effects of the study drug and the way in which the study drug works (mechanism of action), by measuring specific biomarkers in blood and lavage samples and by evaluating changes in lung function measurements. In addition, the trial will assess how safe the drug is and how well the body tolerates the study drug.The clinical trial will comprise a screening period, a treatment period consisting of an outpatient period and an inpatient period, and a follow-up visit. The expected maximum duration of participation for each subject will be approximately 6 weeks.
Eligible subjects will be randomised to receive either the study drug or placebo in a 1:1 ratio. Subjects will receive multiple oral doses of study medication 12-hourly on Days 1 to 5. On Day 5 (4 hours after the morning dose of study medication), subjects will breathe in nebulised LPS, after which lavage samples will be collected. Treatment period assessments will be performed until discharge on Day 6.
The study drug is approved in the United Kingdom and other countries for the treatment of specific types of cancer. With this trial, the Sponsor (Exvastat Ltd.) is investigating the effectiveness of IMATINIB to treat a life threatening condition called acute respiratory distress syndrome (ARDS) for which there currently is no effective pharmacological treatment.
REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
17/EE/0355
Date of REC Opinion
13 Oct 2017
REC opinion
Further Information Favourable Opinion