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Effect of ruboxistaurin (RBX) On visual acuity decline over a 6-year period with cessation and reinstitution of therapy: results of an open-label extension of the Protein Kinase C Diabetic Retinopathy Study 2 (PKC-DRS2).
Retina. 2011 Jun; 31(6):1053-9.R

Abstract

PURPOSE

The PKC-DRS2 was a Phase 3, randomized, double-masked, placebo (PBO)-controlled, 3-year study of the effect of 32 mg/day of ruboxistaurin (RBX), an orally administered protein kinase C inhibitor, on vision loss in patients with moderate to severe nonproliferative diabetic retinopathy. Ruboxistaurin reduced the occurrence of sustained moderate visual loss (SMVL; ≥15-letter decline in visual acuity sustained for the last 6 months of study participation) from 9.1% in the PBO group (N = 340) to 5.5% in the RBX group (N = 345, P = 0.034). This study evaluates the primary end point of SMVL in a 2-year open-label extension (OLE) of the PKC-DRS2, which began a median of 466 days (range, 263-1,296 days) after the conclusion of PKC-DRS2.

METHODS

Visual acuity was measured by certified examiners using the Early Treatment Diabetic Retinopathy Study chart.

RESULTS

Of the 514 patients who completed PKC-DRS2, 366 did so in the 32 study centers participating in the OLE, and of these, 203 (55%) enrolled in the OLE for treatment with 32 mg/day of RBX for 2 years. Of the 203 enrolled in the OLE, 100 had previously been treated with PBO (prior PBO subgroup) and 103 had been treated with RBX (prior RBX subgroup). PKC-DRS2 baseline patient and ocular characteristics were well matched between these two subgroups and were similar to the PKC-DRS2 patient population as a whole. Using the PKC-DRS2 baseline as the starting point, SMVL occurred in 6% of the prior PBO subgroup during the PKC-DRS2, increasing to 26% by the end of the OLE. However, in the prior RBX subgroup, SMVL occurred in only 4% and 8% during the PKC-DRS2 and by the end of the OLE, respectively (P < 0.001 for difference at the end of the OLE). In the prior PBO subgroup, mean visual acuity declined from 79.6 letters at PKC-DRS2 baseline to 73.1 letters at OLE end point (-6.5 letters). In the prior RBX subgroup, this loss was 2.7 letters (79.8 to 77.1) over the same period (P = 0.02).

CONCLUSION

Over a 6-year study period incorporating 3 years of a rigorously placebo-controlled trial, approximately 1 year off treatment and 2-year OLE where all groups received therapy, those patients with greatest RBX exposure (∼5 years) experienced less SMVL compared with those in the original PBO group (∼2-year RBX exposure).

Authors+Show Affiliations

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. msheetz@lilly.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21386766

Citation

Sheetz, Matthew J., et al. "Effect of Ruboxistaurin (RBX) On Visual Acuity Decline Over a 6-year Period With Cessation and Reinstitution of Therapy: Results of an Open-label Extension of the Protein Kinase C Diabetic Retinopathy Study 2 (PKC-DRS2)." Retina (Philadelphia, Pa.), vol. 31, no. 6, 2011, pp. 1053-9.
Sheetz MJ, Aiello LP, Shahri N, et al. Effect of ruboxistaurin (RBX) On visual acuity decline over a 6-year period with cessation and reinstitution of therapy: results of an open-label extension of the Protein Kinase C Diabetic Retinopathy Study 2 (PKC-DRS2). Retina (Philadelphia, Pa). 2011;31(6):1053-9.
Sheetz, M. J., Aiello, L. P., Shahri, N., Davis, M. D., Kles, K. A., & Danis, R. P. (2011). Effect of ruboxistaurin (RBX) On visual acuity decline over a 6-year period with cessation and reinstitution of therapy: results of an open-label extension of the Protein Kinase C Diabetic Retinopathy Study 2 (PKC-DRS2). Retina (Philadelphia, Pa.), 31(6), 1053-9. https://doi.org/10.1097/IAE.0b013e3181fe545f
Sheetz MJ, et al. Effect of Ruboxistaurin (RBX) On Visual Acuity Decline Over a 6-year Period With Cessation and Reinstitution of Therapy: Results of an Open-label Extension of the Protein Kinase C Diabetic Retinopathy Study 2 (PKC-DRS2). Retina (Philadelphia, Pa). 2011;31(6):1053-9. PubMed PMID: 21386766.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of ruboxistaurin (RBX) On visual acuity decline over a 6-year period with cessation and reinstitution of therapy: results of an open-label extension of the Protein Kinase C Diabetic Retinopathy Study 2 (PKC-DRS2). AU - Sheetz,Matthew J, AU - Aiello,Lloyd Paul, AU - Shahri,Nazila, AU - Davis,Matthew D, AU - Kles,Keri A, AU - Danis,Ronald P, AU - ,, PY - 2011/3/10/entrez PY - 2011/3/10/pubmed PY - 2011/11/16/medline SP - 1053 EP - 9 JF - Retina (Philadelphia, Pa.) JO - Retina (Philadelphia, Pa.) VL - 31 IS - 6 N2 - PURPOSE: The PKC-DRS2 was a Phase 3, randomized, double-masked, placebo (PBO)-controlled, 3-year study of the effect of 32 mg/day of ruboxistaurin (RBX), an orally administered protein kinase C inhibitor, on vision loss in patients with moderate to severe nonproliferative diabetic retinopathy. Ruboxistaurin reduced the occurrence of sustained moderate visual loss (SMVL; ≥15-letter decline in visual acuity sustained for the last 6 months of study participation) from 9.1% in the PBO group (N = 340) to 5.5% in the RBX group (N = 345, P = 0.034). This study evaluates the primary end point of SMVL in a 2-year open-label extension (OLE) of the PKC-DRS2, which began a median of 466 days (range, 263-1,296 days) after the conclusion of PKC-DRS2. METHODS: Visual acuity was measured by certified examiners using the Early Treatment Diabetic Retinopathy Study chart. RESULTS: Of the 514 patients who completed PKC-DRS2, 366 did so in the 32 study centers participating in the OLE, and of these, 203 (55%) enrolled in the OLE for treatment with 32 mg/day of RBX for 2 years. Of the 203 enrolled in the OLE, 100 had previously been treated with PBO (prior PBO subgroup) and 103 had been treated with RBX (prior RBX subgroup). PKC-DRS2 baseline patient and ocular characteristics were well matched between these two subgroups and were similar to the PKC-DRS2 patient population as a whole. Using the PKC-DRS2 baseline as the starting point, SMVL occurred in 6% of the prior PBO subgroup during the PKC-DRS2, increasing to 26% by the end of the OLE. However, in the prior RBX subgroup, SMVL occurred in only 4% and 8% during the PKC-DRS2 and by the end of the OLE, respectively (P < 0.001 for difference at the end of the OLE). In the prior PBO subgroup, mean visual acuity declined from 79.6 letters at PKC-DRS2 baseline to 73.1 letters at OLE end point (-6.5 letters). In the prior RBX subgroup, this loss was 2.7 letters (79.8 to 77.1) over the same period (P = 0.02). CONCLUSION: Over a 6-year study period incorporating 3 years of a rigorously placebo-controlled trial, approximately 1 year off treatment and 2-year OLE where all groups received therapy, those patients with greatest RBX exposure (∼5 years) experienced less SMVL compared with those in the original PBO group (∼2-year RBX exposure). SN - 1539-2864 UR - https://www.unboundmedicine.com/medline/citation/21386766/Effect_of_ruboxistaurin__RBX__On_visual_acuity_decline_over_a_6_year_period_with_cessation_and_reinstitution_of_therapy:_results_of_an_open_label_extension_of_the_Protein_Kinase_C_Diabetic_Retinopathy_Study_2__PKC_DRS2__ L2 - http://dx.doi.org/10.1097/IAE.0b013e3181fe545f DB - PRIME DP - Unbound Medicine ER -