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Begona Ruiz-Perez, William Schubert, Tom Sanford, Michael A. Patane; Safety Assessment of 6-Month Dosing of EGP-437 (Dexamethasone Phosphate) Via Ocular Iontophoresis in Rabbits. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4327.
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EGP-437 (dexamethasone phosphate solution tailored for iontophoresis) administered by the EyeGate® II Delivery System (EGDS) has demonstrated safety and efficacy in two Phase II clinical studies. In dry eye patients, EGP-437 significantly improved signs and symptoms during a three-week controlled adverse environment study that included two doses of EGP-437. In anterior uveitis patients, a single EGP-437 treatment rapidly decreased anterior cell counts in the majority of the patients.The present study focuses on assessing chronic ocular and systemic safety of EGP-437 administered by EGDS in rabbits.
New Zealand albino female rabbits received biweekly doses of EGP-437 using the EGDS for 24 weeks (12 doses) at 10 mA-min (3 mA), 14 mA-min (4 mA), or 20 mA-min (4 mA). Similarly control animals received biweekly doses of citrate buffer for 24 weeks (12 doses) at 20 mA-min (4 mA), or 0 mA-min (no current applied). Ocular assessments included weekly ocular exams, semiweekly intraocular pressure (IOP), and electroretinogram (ERG) every 12 weeks. Animals were sacrificed either 1 day (n = 4 per group) or 4 weeks (n = 2 per group) after the last iontophoresis dose. Eyes, brains, and other tissues were histopathologically evaluated.
All treatments were well tolerated. There were no significant clinical observations related to drug or iontophoresis. ~10% of the animals (across all groups) showed slight weight loss (<10%), which may be related to repeated anesthesia. There were no significant macroscopic ocular effects. Mild conjunctival swelling and congestion, and mild to mid corneal fluorescein staining was observed immediately after dosing in all groups (including controls), and resolved in 1 - 7 days. There were no corneal or lens opacities. There were no alterations on IOP or ERG.
Iontophoresis of EGP-437 or citrate buffer at currents to 4 mA and doses to 20 mA-min for 24 weeks (dosed biweekly) was well tolerated. Ocular observations resolved quickly and were similar to those reported in acute studies. Chronic administration of EGP-437 by iontophoresis did not alter IOP or induce cataract formation.
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