Article

The Effect of the Oral PKC beta Inhibitor Ruboxistaurin on Vision Loss in Two Phase 3 Studies

Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, United States.
Investigative ophthalmology & visual science (Impact Factor: 3.43). 02/2013; 54(3). DOI: 10.1167/iovs.12-11055
Source: PubMed

ABSTRACT PURPOSE: To assess the effect of ruboxistaurin (RBX) on vision loss through a prospectively-defined combined analysis of two phase 3 trials (MBDL and MBCU). Methods: Patients in both of these three-year, randomized, placebo controlled, double masked trials had best corrected ETDRS visual acuity (VA) ≥75 letters (~20/32 Snellen), ETDRS retinopathy level 20-47D (MBDL) or 35-53E (MBCU), and no prior panretinal or focal photocoagulation in at least 1 eye at baseline. Patients received oral placebo (N=508 total from both studies) or RBX 32 mg/day (N=520 total). Best-corrected ETDRS VA was measured at 6 month intervals for 3 years (MBDL) or for 18-48 months (MBCU). Sustained moderate visual loss (SMVL) was defined as a 15-letter or more reduction from baseline in VA sustained for a patient's last 6 months of study participation. Results: In the combined studies (N=1028 total), SMVL occurred in 4.4% of placebo- vs 2.3% of RBX treated patients (P=0.069). In patients with a minimum of 2 years of follow-up (N=825 total) there was less SMVL in the RBX group (4.4% placebo vs. 2.1% RBX, p=0.045). Other VA-related measures (mean VA, contrast sensitivity, VFQ-25 questionnaire) either trended towards a benefit for RBX or were also statistically significant in favor of RBX. In contrast, DME morphology-related measures (occurrence of significant center of macula involvement, OCT-determined center of macula thickness, application of focal photocoagulation) did not show a consistent trend in favor of or against RBX. Conclusion: SMVL data in a prospectively defined combined analysis from these two phase 3 trials suggest a similar magnitude of effect of RBX on vision loss as seen in two prior studies (approximately 50% reduction above standard care). However event rates were low and statistical significance was not achieved.

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