Safety Analysis of a Sustained Release Travoprost Intracameral Hydrogel Implant in Beagle Dogs

Abstract

Purpose : To assess the safety of an intracameral hydrogel implant, OTX-TIC, formulated for zero-order travoprost release over 4-months.

Methods : OTX-TIC was injected using a 27 g needle into the anterior chamber of beagle dogs (n=16; 32 eyes); half of the animals received a control article in the right eye and the left eye was untreated. All animals were clinically observed daily, with local toxicity evaluation based on anterior segment ophthalmic examinations, fundus evaluations, intraocular pressure (IOP), measurement of corneal thickness, changes in pupil diameter and histopathology of ophthalmic tissues. Systemic toxicity was evaluated based on survival, clinical signs, body weight, quantitative food consumption, clinical pathology and macroscopic and microscopic findings. Plasma samples were collected pre- and post-dose (1 and 4 hours, and at 2, 4, 6, 8, 10, 12, 14 and 16 weeks) and were analyzed for travoprost (ester and acid) by LC/MS/MS (LOQ 0.5 ng/mL).

Results : Test and placebo articles were well-tolerated over 4 months. No systemic toxicity, changes in corneal thickness, or macro or microscopic findings on histopathology were observed. Plasma values of travoprost were below the LOQ for all samples. The major ocular findings were mild conjunctiva redness (a known effect of travoprost), and mild conjunctival discharge (considered to be injection related and observed in both test and control article treated animals). All mild ocular findings resolved over the course of the study. IOP in eyes injected with OTX-TIC was significantly lower (P<0.05) than in eyes injected with control articles or untreated eyes on Day 120; Correspondingly, pupil size was also decreased in the test articles treated eyes.

Conclusions : These findings are consistent with the known IOP lowering efficacy and miotic response of travoprost. There was no significant difference in corneal thickness between all groups. The histopathological evaluation indicated there were no macroscopic or microscopic findings related to the test article, after 4 months of test article exposure in the eyes of beagle dogs. The presence of the test articles was well tolerated. Results showed no systemic toxicity after administration.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.