September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A 6-Week Toxicity and Toxicokinetics Study of a Single Bilateral Intracameral Administration of ENV905 (difluprednate) Ophthalmic Implant in New Zealand White Rabbits
Author Affiliations & Notes
  • RiLee Robeson
    Ophthalmology, Envisia Therapeutics, Morrisville, North Carolina, United States
  • Rozemarijn S Verhoeven
    Ophthalmology, Envisia Therapeutics, Morrisville, North Carolina, United States
  • Andres Garcia
    Ophthalmology, Envisia Therapeutics, Morrisville, North Carolina, United States
  • Paul Miller
    OSOD, Madison, Wisconsin, United States
  • Jacqueline Miller
    Covance Laboratories, Madison, Wisconsin, United States
  • Tomas Navratil
    Ophthalmology, Envisia Therapeutics, Morrisville, North Carolina, United States
  • Rhett M Schiffman
    Ophthalmology, Envisia Therapeutics, Morrisville, North Carolina, United States
  • Footnotes
    Commercial Relationships   RiLee Robeson, None; Rozemarijn Verhoeven, Envisia Therapeutics (P); Andres Garcia, Envisia Therapeutics (P); Paul Miller, None; Jacqueline Miller, None; Tomas Navratil, None; Rhett Schiffman, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4013. doi:
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      RiLee Robeson, Rozemarijn S Verhoeven, Andres Garcia, Paul Miller, Jacqueline Miller, Tomas Navratil, Rhett M Schiffman; A 6-Week Toxicity and Toxicokinetics Study of a Single Bilateral Intracameral Administration of ENV905 (difluprednate) Ophthalmic Implant in New Zealand White Rabbits. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4013.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To evaluate the ocular and systemic toxicity and toxicokinetics of a single bilateral administration of ENV905 in rabbits. ENV905 is being developed as a treatment for inflammation and pain associated with ocular surgery.

Methods : Male and female NZW rabbits (3/sex/group/terminal time point) were administered a single bilateral intracameral administration of ENV905 (up to 3 implants/eye) or placebo and were followed for up to 6 weeks. Animals were evaluated for standard toxicology endpoints as well as ophthalmic examinations, intraocular pressure (IOP), corneal thickness, electroretinography (ERG), plasma bioanalysis, and histopathology, and were sacrificed on Days 2 or 43.

Results : There were no adverse test-article related effects on mortality, clinical observations, food consumption, body weights, slit lamp and indirect ophthalmoscopy, IOP, corneal thickness, or macroscopic findings at necropsy. Animals given ENV905 displayed a decrease in procedure-associated ocular inflammation on Days 2 and 3 compared with control. Mild and reversible clinical pathology and systemic histopathology findings were consistent with glucocorticoid administration. Ocular histopathology findings were limited to a decrease in ocular mixed cell inflammation and heterophilic infiltrates compared with control on Day 2, demonstrating a dampening effect on inflammation associated with the dosing procedure. Plasma concentration of desacetyl difluprednate (DFB) peaked at 2 hours post-dose in all ENV905 groups, with mean Cmax=2.5 ng/mL in the high dose group, and was not quantifiable after Day 4.

Conclusions : A single bilateral intracameral administration of ENV905 was well tolerated in the NZW rabbit over 6 weeks, and systemic exposure to DFB was minimal. Test article-related findings were limited to mild effects associated with glucocorticoids as well as a dampening of inflammation associated with the dosing procedure. The no observed adverse effect level (NOAEL) for ENV905 in this GLP study was the high dose of 3 implants/eye.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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