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P. B. Williams, F. A. Lattanzio, Jr., S. S. Samudre, A. Hosseini, C. M. Greven, J. L. Jacot; Absence of Adverse Effects Following 6 Months Topical Application of OC-10X. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2974.
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OC-10X, a tubulin inhibitor, is an efficacious antiangiogenic compound. Systemic treatment with tubulin inhibitors is associated with adverse effects (AEs). Long-term application of OC-10X for therapeutic use was evaluated by ocular tolerability, complete blood clinical chemistry panel (CBCP), complete blood count (CBC), necropsy of major organs, full field electroretinogram (ffERG) for retinal status, and visual assessment of ocular tissue.
1% OC-10X suspension or vehicle eye drops were administered bilaterally 3 times/day to male S-D rats (n=3/gp) for 6 months. Rats were weighed weekly as an index of general health. Ocular tolerability was evaluated using a modified categorical scale for irritation and toxicity of topically applied drugs (0=well tolerated, poorly tolerated max=50). After 3 and 6 months dark-adapted ffERGs were performed and tail vein blood collected for CBCP and CBC. Major organs were evaluated at necropsy.
All rats had normal weight gain. Evaluation of ocular tolerability included absence of cataracts, corneal opacities, inflammation (new blood vessels), epithelial irregularity and conjunctival redness/irritation. The tolerability score for the OC-10X group at baseline was 0.36±1.18, 3 mo 0±0, and 6 mo 0±0. The vehicle group score was baseline 1.27±1.16, 3 mo 0±0, 6 mo 0±0. There were no differences in the magnitude of the a-b wave of the ffERG between the treated and vehicle groups. There were no differences in the CBCP or CBC between groups. After 3 months, all organs were normal by necropsy; after 6 months slight adrenal enlargement and GI mucosal irritation was noted in some rats irrespective of treatment group.
Visual assessment for ocular tolerability and necropsy for AEs indicated that OC-10X had no deleterious effects on tissue structure. Likewise, ffERG, CBC and CBCP found no evidence of major organ dysfunction. Absence of structural and functional toxic effects suggests that topical treatment with OC-10X suspension can be safely administered for extended periods such as may be required by patients with AMD.
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