emixustat and Diabetic-Retinopathy

To evaluate the effects of oral emixustat hydrochloride on pro-angiogenic and inflammatory cytokines in the aqueous humor, as well as other ophthalmic parameters, in subjects with proliferative diabetic retinopathy (PDR).. Twenty-three patients with PDR, with or without diabetic macular edema (DME), were assigned to emixustat or placebo in daily oral doses ranging from 5 to 40 mg over a step-up titration period, for 84 days. The main outcome measures included levels of IL-1β, IL-6, IL-8, TGFβ-1, and VEGF in the aqueous humor.. Seven of 12 subjects (58%) who were randomized to emixustat and 11 of 12 subjects (92%) who were randomized to placebo completed the study. No statistically significant differences between treatment groups were observed for changes in any of the aqueous humor cytokines tested. However, median VEGF levels were slightly reduced in the emixustat but not the placebo group (- 70.0 pg/mL versus + 42.7 pg/mL, or - 11.8% versus + 6.7%). In a post hoc analysis of all subjects (with or without DME), statistically significant differences between treatment arms in mean changes from baseline in central subfield thickness (CST; emixustat - 11.9 μm, placebo + 36.2 μm; P = 0.076) and total macular volume (TMV; emixustat - 0.13 mm. Although this pilot study did not demonstrate statistically significant differences in changes in aqueous humor cytokine levels between the emixustat and placebo groups, VEGF levels were slightly reduced in the emixustat but not in the placebo group. In addition, statistically significant differences favoring the emixustat group were observed in CST and TMV among all subjects. These data warrant further investigation of emixustat's potential therapeutic effects in diabetic retinopathy.. ClinicalTrials.gov identifier: NCT02753400 (April 2016).

Topics: Angiogenesis Inhibitors; Aqueous Humor; Diabetes Mellitus; Diabetic Retinopathy; Humans; Macular Edema; Phenyl Ethers; Pilot Projects; Propanolamines; Vascular Endothelial Growth Factor A