Imperial College London
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ProfessorPhilipMolyneaux

Faculty of Medicine, National Heart & Lung Institute

Professor of Interstitial Lung Disease
 
 
 
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Contact

 

p.molyneaux

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lukey:2019:10.1183/13993003.01992-2018,
author = {Lukey, PT and Harrison, SA and Yang, S and Man, Y and Holman, BF and Rashidnasab, A and Azzopardi, G and Grayer, M and Simpson, JK and Bareille, P and Paul, L and Woodcock, HV and Toshner, R and Saunders, P and Molyneaux, PL and Thielemans, K and Wilson, FJ and Mercer, PF and Chambers, RC and Groves, AM and Fahy, WA and Marshall, RP and Maher, TM},
doi = {10.1183/13993003.01992-2018},
journal = {European Respiratory Journal},
title = {A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis},
url = {http://dx.doi.org/10.1183/13993003.01992-2018},
volume = {53},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - PI3 Kinases (PI3Ks) and mammalian target of rapamycin (mTOR) play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Omipalisib (GSK2126458) is a potent inhibitor of PI3K/mTOR.A randomised, placebo-controlled, double-blind, repeat dose escalation, experimental medicine study of omipalisib in subjects with IPF was conducted (NCT01725139) to test safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD). Omipalisib was dosed, at 0.25mg, 1mg and 2mg twice per day (BID) for approximately eight days in 4 cohorts of 4 subjects randomised 3:1 to receive omipalisib or placebo (two cohorts received 2mg BID).Seventeen subjects with IPF were enrolled. The most common adverse event was diarrhoea, which was reported by four participants. Dose related increases in insulin and glucose were observed. PK analysis demonstrated that exposure in the blood predicts lung exposure. Exposure dependent inhibition of PIP3 and pAKT confirmed target engagement in blood and lungs. [18F]-FDG-PET/CT scans revealed an exposure dependent reduction in [18F]-FDG uptake in fibrotic areas of the lung, as measured by target to background ratio (TBR) thus confirming pharmacodynamic activity.This experimental medicine study demonstrates acceptable tolerability of omipalisib in subjects with IPF at exposures for which target engagement was confirmed both systemically and in the lungs.
AU  - Lukey,PT
AU  - Harrison,SA
AU  - Yang,S
AU  - Man,Y
AU  - Holman,BF
AU  - Rashidnasab,A
AU  - Azzopardi,G
AU  - Grayer,M
AU  - Simpson,JK
AU  - Bareille,P
AU  - Paul,L
AU  - Woodcock,HV
AU  - Toshner,R
AU  - Saunders,P
AU  - Molyneaux,PL
AU  - Thielemans,K
AU  - Wilson,FJ
AU  - Mercer,PF
AU  - Chambers,RC
AU  - Groves,AM
AU  - Fahy,WA
AU  - Marshall,RP
AU  - Maher,TM
DO  - 10.1183/13993003.01992-2018
PY  - 2019///
SN  - 0903-1936
TI  - A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis
T2  - European Respiratory Journal
UR  - http://dx.doi.org/10.1183/13993003.01992-2018
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30765508
UR  - http://hdl.handle.net/10044/1/68165
VL  - 53
ER  -
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