Objective: To evaluate the safety and efficacy of orally administered ruboxistaurin (RBX) as a mesylate salt in patients with diabetic macular edema (DME).
Design: Multicenter, double-masked, randomized, placebo-controlled study of 686 patients receiving placebo or RBX orally (4, 16, or 32 mg/d) for 30 months. At baseline, patients had DME farther than 300 mum from the center of the macula, an Early Treatment Diabetic Retinopathy Study retinopathy severity level from 20 to 47A without prior photocoagulation, and an Early Treatment Diabetic Retinopathy Study visual acuity of 75 or more letters in the study eye. The primary study outcome was progression to sight-threatening DME or application of focal/grid photocoagulation for DME. Main Outcome Measure Masked grading of stereoscopic fundus photographs.
Results: The delay in progression to the primary outcome was not statistically significant (32 mg of RBX vs placebo, P = .14 [unadjusted]; Cox proportional hazards model adjusted for covariates, hazards ratio = 0.73; 95% confidence interval, 0.53-1.0; P = .06). However, application of focal/grid photocoagulation prior to progression to sight-threatening DME varied by site, and a secondary analysis of progression to sight-threatening DME alone showed that 32 mg of RBX per day reduced progression, compared with placebo (P = .054 [unadjusted]; Cox proportional hazards model, hazards ratio = 0.66; 95% confidence interval, 0.47-0.93; P = .02).
Conclusions: Although progression to the primary outcome was not delayed, daily oral administration of RBX may delay progression of DME to a sight-threatening stage. Ruboxistaurin was well tolerated in this study.