The Developing Regorafenib Eye drops for neovascular Age-related Macular degeneration (DREAM) study: an open-label phase II trial.
Administration, Ophthalmic
Aged
Aged, 80 and over
Angiogenesis Inhibitors
/ administration & dosage
Female
Humans
Macular Degeneration
/ drug therapy
Male
Ophthalmic Solutions
/ administration & dosage
Phenylurea Compounds
/ administration & dosage
Pyridines
/ administration & dosage
Treatment Outcome
Visual Acuity
/ drug effects
clinical trials
drug development
ophthalmology
pharmacometrics
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
16
01
2018
revised:
02
10
2018
accepted:
12
10
2018
pubmed:
21
10
2018
medline:
4
3
2020
entrez:
21
10
2018
Statut:
ppublish
Résumé
This programme investigated topical regorafenib, a multikinase inhibitor, in patients with neovascular age-related macular degeneration (nAMD). Topical regorafenib was investigated in an open-label, phase IIa/b study in which patients with choroidal neovascularization (CNV) secondary to nAMD received regorafenib (25 μl, 30 mg ml In nAMD patients (N = 51), mean changes in BCVA were +1.2 [90% confidence interval (CI) -0.61, 2.97] and -2.4 (90% CI -4.18, -0.54) letters at weeks 4 and 12, respectively. Ocular treatment-emergent adverse events (TEAEs) (study eye) were reported in 21 patients by week 12. There was one serious ocular TEAE (visual acuity reduced) that was not drug related. Twenty patients required rescue (intravitreal ranibizumab). The programme was terminated after phase IIa ended because efficacy was lower than with current nAMD treatments. According to elaborate post hoc analyses, the most likely reason was insufficient exposure in the target compartment (back of the eye).
Identifiants
pubmed: 30341774
doi: 10.1111/bcp.13794
pmc: PMC6339971
doi:
Substances chimiques
Angiogenesis Inhibitors
0
Ophthalmic Solutions
0
Phenylurea Compounds
0
Pyridines
0
regorafenib
24T2A1DOYB
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
347-355Informations de copyright
© 2018 The British Pharmacological Society.
Références
Ophthalmology. 2014 Jan;121(1):193-201
pubmed: 24084500
Eye (Lond). 2011 Jun;25(6):661-72
pubmed: 21455242
Nucleic Acids Res. 2018 Jan 4;46(D1):D1091-D1106
pubmed: 29149325
Biochem Biophys Res Commun. 2008 Oct 24;375(3):287-91
pubmed: 18680722
Ophthalmology. 2012 Dec;119(12):2537-48
pubmed: 23084240
Lancet. 2013 Oct 12;382(9900):1258-67
pubmed: 23870813
Exp Eye Res. 2016 Apr;145:373-379
pubmed: 26927930
Lancet. 2013 Jan 26;381(9863):295-302
pubmed: 23177515
N Engl J Med. 2011 May 19;364(20):1897-908
pubmed: 21526923
Int J Biochem Cell Biol. 2007;39(7-8):1349-57
pubmed: 17537667
N Engl J Med. 2006 Oct 5;355(14):1419-31
pubmed: 17021318
Invest Ophthalmol Vis Sci. 1999 Aug;40(9):2115-21
pubmed: 10440268
Klin Monbl Augenheilkd. 2013 Mar;230(3):247-54
pubmed: 23508753
Jpn J Ophthalmol. 1982;26(3):248-63
pubmed: 6130180
Ophthalmology. 2012 Jul;119(7):1388-98
pubmed: 22555112
Biol Pharm Bull. 2008 May;31(5):970-5
pubmed: 18451528
Arch Ophthalmol. 2011 Aug;129(8):1042-52
pubmed: 21825187
Toxicol In Vitro. 2008 Mar;22(2):457-67
pubmed: 17981004
Ophthalmology. 2009 Jan;116(1):57-65.e5
pubmed: 19118696
Br J Clin Pharmacol. 2018 May;84(5):865-875
pubmed: 29315699
Int J Cancer. 2011 Jul 1;129(1):245-55
pubmed: 21170960
Invest Ophthalmol Vis Sci. 2000 Oct;41(11):3582-9
pubmed: 11006256
N Engl J Med. 2006 Oct 5;355(14):1432-44
pubmed: 17021319
Ophthalmology. 2012 Jul;119(7):1399-411
pubmed: 22578446
Am J Pathol. 2006 Jun;168(6):2036-53
pubmed: 16723717
Arch Ophthalmol. 1989 Feb;107(2):264-9
pubmed: 2464985
Ophthalmology. 2015 Mar;122(3):579-88
pubmed: 25432081
Invest Ophthalmol Vis Sci. 1987 Mar;28(3):487-91
pubmed: 3557861
Am J Pathol. 1997 Jul;151(1):13-23
pubmed: 9212726
Br J Pharmacol. 2017 Dec;174 Suppl 1:S225-S271
pubmed: 29055036
Invest Ophthalmol Vis Sci. 2002 Mar;43(3):849-57
pubmed: 11867607
Br J Clin Pharmacol. 2019 Feb;85(2):347-355
pubmed: 30341774
Clin Cancer Res. 2012 May 1;18(9):2658-67
pubmed: 22421192