Effect of Hydrogel Persistence on Pharmacodynamics and Tolerability of OTX-TIC, Travoprost Intracameral Implant in Beagles

Abstract

Purpose : To evaluate the effect of hydrogel persistence on the pharmacodynamics and tolerability of OTX-TIC, a resorbable travoprost sustained release hydrogel-based implant administered intracamerally into the anterior chamber (AC). OTX-TIC is a potential new therapy to treat glaucoma and is currently being evaluated in a Phase 1 clinical trial.

Methods : Two OTX-TIC hydrogel matrices containing travoprost particles were formulated with a hydrogel persistence of 8 (shorter persisting hydrogel) and 16 weeks (longer persisting hydrogel). Each OTX-TIC formulation was injected bilaterally (OU) into the anterior chamber of 3 beagles. Measurements of intraocular pressure (IOP) using a TonoVet® tonometer, pupil diameter using an embossed pictorial scale on a penlight, central corneal thickness (CCT) and corneal endothelial cell density (ECD) using an automated specular microscope (CellChek CL) were captured at predetermined timepoints over 20 weeks.

Results : The shorter persisting OTX-TIC implant residing in the inferior iridocorneal angle of the AC degraded completely by 8 weeks, while the longer persisting implant degraded by 20 weeks. IOP lowering effect and pupil constriction was consistent for both OTX-TIC formulations until 16 weeks (Table 1). No statistically significant changes compared to baseline were noted in CCT or ECD over 20 weeks (Table 2).

Conclusions : Persistence of the OTX-TIC hydrogel matrix in the AC does not impact the sustained release of travoprost as indicated by the consistent pupil constriction and IOP lowering effect of the two formulations. Although shorter persisting hydrogel degraded by 8 weeks, IOP control and pupil constriction induced by the sustained release travoprost lasted until 16 weeks. The release of travoprost is controlled by the encapsulated travoprost particles dispersed from the hydrogel matrix into the anterior chamber over time. No clinically significant change was observed in CCT or ECD over the course of the study indicating no damage to the corneal endothelium due to the implant.

This is a 2020 ARVO Annual Meeting abstract.

 

Mean IOP change from baseline and pupil diameter after OTX-TIC administration in beagles (n=6 eyes) over 20 weeks

 

Mean CCT and ECD after OTX-TIC administration in beagles (n=6 eyes) over 20 weeks