PMID- 25749297 OWN - NLM STAT- MEDLINE DCOM- 20150716 LR - 20220317 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 122 IP - 5 DP - 2015 May TI - Darapladib, a lipoprotein-associated phospholipase A2 inhibitor, in diabetic macular edema: a 3-month placebo-controlled study. PG - 990-6 LID - S0161-6420(14)01191-9 [pii] LID - 10.1016/j.ophtha.2014.12.014 [doi] AB - PURPOSE: 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). DESIGN: Prospective, multicenter, randomized, double-masked, placebo-controlled phase IIa study. PARTICIPANTS: Fifty-four center-involved DME patients randomized 2:1 to receive darapladib (n = 36) or placebo (n = 18). METHODS: Darapladib 160 mg or placebo monotherapy was administered orally once daily for 3 months, and patients were followed up monthly for 4 months. MAIN OUTCOME MEASURES: 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. RESULTS: 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 mum in central subfield thickness (95% CI, -84 to -30) in the study eyes. An increase in BCVA of 1.7 ETDRS letters (95% CI, -1.0 to 4.4) and a decrease in center subfield thickness of 34 mum (95% CI, -75 to 6.8) for the placebo group were not significant. No ocular severe adverse events (SAEs) or SAEs considered related to darapladib were reported. One SAE of myocardial infarction, not considered related to darapladib, was reported, and 1 SAE of severe diarrhea was reported in a placebo patient, subsequently withdrawn from the study. Study eye ocular adverse events (AEs) and nonocular AEs were similar between treatment groups. CONCLUSIONS: Once-daily oral darapladib administered for 3 months demonstrated modest improvements in vision and macular edema that warrant additional investigation of this novel lipoprotein-associated phospholipase A2 inhibitory mechanism for the treatment of DME. CI - Copyright (c) 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Staurenghi, Giovanni AU - Staurenghi G AD - Department of Biomedical and Clinical Science "Luigi Sacco," Sacco Hospital, University of Milan, Milan, Italy. Electronic address: giovanni.staurenghi@unimi.it. FAU - Ye, Li AU - Ye L AD - GlaxoSmithKline, King of Prussia, Pennsylvania. FAU - Magee, Mindy H AU - Magee MH AD - GlaxoSmithKline, King of Prussia, Pennsylvania. FAU - Danis, Ronald P AU - Danis RP AD - Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin. FAU - Wurzelmann, John AU - Wurzelmann J AD - GlaxoSmithKline, Research Triangle Park, North Carolina. FAU - Adamson, Peter AU - Adamson P AD - GlaxoSmithKline, Stevenage, United Kingdom. FAU - McLaughlin, Megan M AU - McLaughlin MM AD - GlaxoSmithKline, King of Prussia, Pennsylvania. CN - Darapladib DME Study Group LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20150305 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 0 (Benzaldehydes) RN - 0 (Oximes) RN - 0 (Phospholipase A2 Inhibitors) RN - UI1U1MYH09 (darapladib) SB - IM MH - Administration, Oral MH - Benzaldehydes/adverse effects/pharmacokinetics/*therapeutic use MH - Chromatography, High Pressure Liquid MH - Diabetic Retinopathy/*drug therapy/metabolism/physiopathology MH - Double-Blind Method MH - Female MH - Humans MH - Macular Edema/*drug therapy/metabolism/physiopathology MH - Male MH - Middle Aged MH - Oximes/adverse effects/pharmacokinetics/*therapeutic use MH - Phospholipase A2 Inhibitors/adverse effects/pharmacokinetics/*therapeutic use MH - Prospective Studies MH - Tandem Mass Spectrometry MH - Visual Acuity/physiology EDAT- 2015/03/10 06:00 MHDA- 2015/07/17 06:00 CRDT- 2015/03/10 06:00 PHST- 2014/07/28 00:00 [received] PHST- 2014/11/20 00:00 [revised] PHST- 2014/12/12 00:00 [accepted] PHST- 2015/03/10 06:00 [entrez] PHST- 2015/03/10 06:00 [pubmed] PHST- 2015/07/17 06:00 [medline] AID - S0161-6420(14)01191-9 [pii] AID - 10.1016/j.ophtha.2014.12.014 [doi] PST - ppublish SO - Ophthalmology. 2015 May;122(5):990-6. doi: 10.1016/j.ophtha.2014.12.014. Epub 2015 Mar 5.