Abstract
To investigate the potential of lipoprotein-associated phospholipase A2 inhibition as a novel mechanism to reduce edema and improve vision in center-involved diabetic macular edema (DME). Prospective, multicenter, randomized, double-masked, placebo-controlled phase IIa study. Fifty-four center-involved DME patients randomized 2:1 to receive darapladib (n = 36) or placebo (n = 18). Darapladib 160 mg or placebo monotherapy was administered orally once daily for 3 months, and patients were followed up monthly for 4 months. Mean change from baseline in best-corrected visual acuity (BCVA) and the center subfield and center point of the study eye at month 3 as determined by spectral-domain optical coherence tomography. Five patients in the study received intravitreal anti-vascular endothelial growth factor rescue therapy before the day 90 assessment, 2 of 36 (6%) in the darapladib arm and 3 of 18 (17%) in the placebo arm. Administration of 160 mg darapladib for 3 months resulted in statistically significant mean improvements, from baseline to month 3, in BCVA of 4.1 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (95% confidence interval [CI], 2.3-5.8) and of 57 μm in central subfield thickness (95% CI, -84 to -30) in the ...Continue Reading
References
Feb 20, 1999·The Biochemical Journal·C H MacPheeD M Hickey
Feb 5, 2003·American Journal of Ophthalmology·Roy W BeckRaymond T Kraker
Mar 20, 2003·Bioorganic & Medicinal Chemistry Letters·Josie A BlackieColin J Theobald
Apr 3, 2004·American Journal of Ophthalmology·Amod GuptaAnil Bhansali
Oct 11, 2005·Surgery·Shaoyu YanChangyi Chen
Dec 3, 2005·Endocrinology·Yoshiko FujitaToshiaki Tamaki
Aug 29, 2006·Diabetes·David A AntonettiUNKNOWN JDRF Diabetic Retinopathy Center Group
Mar 14, 2007·Atherosclerosis·Masanori IwaseMitsuo Iida
May 16, 2007·Circulation·Shahar LaviAmir Lerman
Apr 26, 2008·Journal of the American College of Cardiology·Emile R MohlerUNKNOWN Darapladib Investigators
Sep 23, 2008·Nature Medicine·Robert L WilenskyColin H Macphee
Jan 3, 2009·Ophthalmology·Hideharu FunatsuSadao Hori
May 16, 2009·Eye·T M CurtisA W Stitt
Dec 10, 2009·PloS One·Takeru YoshimuraTatsuro Ishibashi
Jan 5, 2010·Ophthalmology·Rajiv RamanTarun Sharma
Apr 30, 2010·Ophthalmology·UNKNOWN Diabetic Retinopathy Clinical Research NetworkJennifer K Sun
May 29, 2010·Ophthalmic Surgery, Lasers & Imaging : the Official Journal of the International Society for Imaging in the Eye·Theonitsa D PanagiotoglouMiltiadis K Tsilimbaris
Jul 26, 2011·American Journal of Ophthalmology·Hee Jin SohnDong Heun Nam
Aug 25, 2011·Investigative Ophthalmology & Visual Science·Rehab BenarousEcosse L Lamoureux
Feb 4, 2012·Diabetes Care·Joanne W Y YauUNKNOWN Meta-Analysis for Eye Disease (META-EYE) Study Group
Feb 15, 2012·Ophthalmology·Quan Dong NguyenUNKNOWN RISE and RIDE Research Group
Apr 14, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Isabel GonçalvesJan Nilsson
Apr 1, 2014·The New England Journal of Medicine·Harvey D WhiteLars Wallentin
Citations
Mar 2, 2016·Journal of Medicinal Chemistry·Xinde ChenJianhua Shen
Oct 20, 2015·Journal of Medicinal Chemistry·Xinde ChenJianhua Shen
Apr 15, 2016·Journal of Medicinal Chemistry·Qiufeng LiuYe-Chun Xu
May 12, 2016·Journal of Medicinal Chemistry·Alison J-A WoolfordRen Xie
Jun 15, 2016·Proceedings of the National Academy of Sciences of the United States of America·Paul CanningAlan W Stitt
Apr 7, 2018·Diabetologia·Moneeza K SiddiquiColin N A Palmer
Aug 3, 2017·Medicine·Hai-Bing JuHai-Yan Zhang
Nov 6, 2018·Chemistry : a European Journal·Gemma M LockeMathias O Senge
May 30, 2019·Medicinal Research Reviews·Fubao HuangJianhua Shen
Oct 16, 2019·Inflammopharmacology·Benjamin G SpencerJohn W Finnie
Mar 17, 2017·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Nimish K AcharyaRobert G Nagele
Jun 22, 2018·International Journal of Molecular Sciences·Wei Wang, Amy C Y Lo
Jun 30, 2015·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Gareth Maher-EdwardsAndrew Lockhart
Dec 6, 2018·International Journal of Molecular Sciences·Effat AlizadehHelder André
Sep 12, 2019·Current Diabetes Reports·Avinash HonasogeRithwick Rajagopal
Mar 25, 2019·Diabetes Research and Clinical Practice·Yun HuJian-Hua Ma
Feb 18, 2020·Current Diabetes Reviews·Kaveri M Adki, Yogesh A Kulkarni
Jun 19, 2021·Expert Opinion on Drug Discovery·Charikleia S BatsikaGeorge Kokotos
Jul 17, 2021·Acta Ophthalmologica·Karen FruddPatric Turowski
Dec 10, 2016·Journal of Medicinal Chemistry·Alison J-A WoolfordXiaomin Zhang
Dec 2, 2017·Journal of Medicinal Chemistry·Qiufeng LiuYechun Xu
Aug 25, 2021·Journal of Cachexia, Sarcopenia and Muscle·Pauline MorignyMauricio Berriel Diaz
Jan 21, 2017·ACS Medicinal Chemistry Letters·Nicholas D MeasomDon O Somers
Jul 7, 2021·Acta Pharmacologica Sinica·Si-Lin LvMin Yang