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The effect of the oral PKC β inhibitor ruboxistaurin on vision loss in two phase 3 studies.
Invest Ophthalmol Vis Sci. 2013 Mar 11; 54(3):1750-7.IO

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 3-year randomized, placebo-controlled, double-masked trials had best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) ≥ 75 letters (∼20/32 Snellen), ETDRS retinopathy level 20 to 47D (MBDL) or 35B to 53E (MBCU), and no prior panretinal or focal photocoagulation in at least one eye at baseline. Patients received oral placebo (N = 508 total from both studies) or RBX 32 mg/d (N = 520 total). Best-corrected ETDRS VA was measured at 6-month intervals for 3 years (MBDL) or for 18 to 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- versus 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 versus 2.1% RBX, P = 0.045). Other VA-related measures (mean VA, contrast sensitivity, Visual Functioning Questionnaire 25 [VFQ-25]) either trended toward a benefit for RBX or were also statistically significant in favor of RBX. In contrast, diabetic macular edema (DME) morphology-related measures (occurrence of significant center of macula involvement, optical coherence tomography [OCT]-determined center of macula thickness, application of focal photocoagulation) did not show a consistent trend in favor of or against RBX.

CONCLUSIONS

SMVL data in a prospectively defined combined analysis from these two phase 3 trials suggest a magnitude of effect of RBX on vision loss similar to that seen in two prior studies (approximately 50% reduction above standard care). However, event rates were low and statistical significance was not achieved. (ClinicalTrials.gov numbers, NCT00133952, NCT00090519.).

Authors+Show Affiliations

Eli Lilly and Company, Indianapolis, IN 46285, USA. msheetz@lilly.comNo affiliation info availableNo affiliation info availableNo 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

23404115

Citation

Sheetz, Matthew J., et al. "The Effect of the Oral PKC Β Inhibitor Ruboxistaurin On Vision Loss in Two Phase 3 Studies." Investigative Ophthalmology & Visual Science, vol. 54, no. 3, 2013, pp. 1750-7.
Sheetz MJ, Aiello LP, Davis MD, et al. The effect of the oral PKC β inhibitor ruboxistaurin on vision loss in two phase 3 studies. Invest Ophthalmol Vis Sci. 2013;54(3):1750-7.
Sheetz, M. J., Aiello, L. P., Davis, M. D., Danis, R., Bek, T., Cunha-Vaz, J., Shahri, N., & Berg, P. H. (2013). The effect of the oral PKC β inhibitor ruboxistaurin on vision loss in two phase 3 studies. Investigative Ophthalmology & Visual Science, 54(3), 1750-7. https://doi.org/10.1167/iovs.12-11055
Sheetz MJ, et al. The Effect of the Oral PKC Β Inhibitor Ruboxistaurin On Vision Loss in Two Phase 3 Studies. Invest Ophthalmol Vis Sci. 2013 Mar 11;54(3):1750-7. PubMed PMID: 23404115.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of the oral PKC β inhibitor ruboxistaurin on vision loss in two phase 3 studies. AU - Sheetz,Matthew J, AU - Aiello,Lloyd Paul, AU - Davis,Matthew D, AU - Danis,Ronald, AU - Bek,Toke, AU - Cunha-Vaz,Jose, AU - Shahri,Nazila, AU - Berg,Paul H, AU - ,, Y1 - 2013/03/11/ PY - 2013/2/14/entrez PY - 2013/2/14/pubmed PY - 2013/4/25/medline SP - 1750 EP - 7 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 54 IS - 3 N2 - 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 3-year randomized, placebo-controlled, double-masked trials had best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) ≥ 75 letters (∼20/32 Snellen), ETDRS retinopathy level 20 to 47D (MBDL) or 35B to 53E (MBCU), and no prior panretinal or focal photocoagulation in at least one eye at baseline. Patients received oral placebo (N = 508 total from both studies) or RBX 32 mg/d (N = 520 total). Best-corrected ETDRS VA was measured at 6-month intervals for 3 years (MBDL) or for 18 to 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- versus 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 versus 2.1% RBX, P = 0.045). Other VA-related measures (mean VA, contrast sensitivity, Visual Functioning Questionnaire 25 [VFQ-25]) either trended toward a benefit for RBX or were also statistically significant in favor of RBX. In contrast, diabetic macular edema (DME) morphology-related measures (occurrence of significant center of macula involvement, optical coherence tomography [OCT]-determined center of macula thickness, application of focal photocoagulation) did not show a consistent trend in favor of or against RBX. CONCLUSIONS: SMVL data in a prospectively defined combined analysis from these two phase 3 trials suggest a magnitude of effect of RBX on vision loss similar to that seen in two prior studies (approximately 50% reduction above standard care). However, event rates were low and statistical significance was not achieved. (ClinicalTrials.gov numbers, NCT00133952, NCT00090519.). SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/23404115/The_effect_of_the_oral_PKC_β_inhibitor_ruboxistaurin_on_vision_loss_in_two_phase_3_studies_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.12-11055 DB - PRIME DP - Unbound Medicine ER -