Abstract
Abstract: :
Purpose: To evaluate the efficacy and safety of oral PKC412 in patients with diabetic macular edema (DME). Methods: A total of 141 patients with DME were randomized to receive PKC412 (50, 100, or 150 mg/day) or placebo twice daily for 3 months, with a 12-month follow-up period after drug treatment. The macula was divided into 13 locations for evaluation of retinal thickening. Changes from the baseline area of retinal thickening, central involvement of the macula, and ETDRS classification of diabetic retinopathy were assessed using fundus photos. Other evaluations included change from baseline in visual acuity (VA), assessment of fluorescein angiograms, and contrast sensitivity. Retinal thickness was assessed using Optical Coherence Tomography (OCT) in 55 patients. An interim analysis of Month 3 data, when all patients had completed treatment, is presented. The difference between treatment groups for change from Baseline was tested using an analysis of covariance model, with statistical significance declared at P ≤ 0.048. Results: At baseline, assessment of the area of retinal thickening by fundus photos, and retinal thickness by OCT, showed significantly smaller values in the placebo group and larger values in the 100 mg/day group. At Month 3, fundus photos showed significant reduction in the area of greatest retinal thickening at 150 mg/day for all locations in the macula combined. Both the 100 mg/day and 150 mg/day doses significantly reduced OCT retinal thickness in the center-center location, as well as in many other locations. The 100 mg/day group also showed a significant improvement in mean VA (>4 letters) and had the most patients (16.67%) with VA improvement of ≥10 letters. Notable drug effects on the other parameters evaluated were not observed. Clinically significant adverse events (AEs) related to PKC412 included nausea, vomiting, diarrhea (mostly at 150 mg/day). Elevated ALT in 10/107 patients, and AST in 7/107 patients, had a suspected relationship to PKC412. Six patients were withdrawn from the study due to AEs related to PKC412. Conclusions: These preliminary results suggest a beneficial effect of PKC412 in DME.
Keywords: diabetic retinopathy • drug toxicity/drug effects • clinical (human) or epidemiologic studies: tre