<p>Loteprednol etabonate (submicron) ophthalmic gel 0.38% dosed three times daily following cataract surgery: integrated analysis of two Phase III clinical studies</p>

Abstract

Purpose To evaluate the efficacy and safety of a submicron formulation of loteprednol etabonate (LE) gel 0.38% instilled three times daily (TID) compared with vehicle for the treatment of inflammation and pain following cataract surgery with intraocular lens implantation, integrated across two multicenter, double-masked, randomized, parallel-group, Phase III studies. Patients and methods Subjects ≥18 years of age with anterior chamber (AC) cells ≥grade 2 (6–15 cells) on day 1 after cataract surgery were randomized to receive 1 drop of LE gel 0.38% TID, twice daily (not reported/analyzed herein), or vehicle instilled in the study eye for 14 days. Primary endpoints were the proportion of subjects with resolution of AC cells and grade 0 (no) pain at postoperative day 8. Safety outcomes included adverse events (AEs), ocular signs, fundoscopy results, visual acuity, intraocular pressure (IOP), and tolerability (drop comfort and ocular symptoms). Results The integrated intent-to-treat population included 742 subjects (LE gel 0.38% TID, n=371; vehicle, n=371). Significantly more subjects in the LE gel 0.38% TID group compared with the vehicle group had complete resolution of AC cells (29.6% vs 15.1%) and grade 0 pain (74.4% vs 48.8%) at day 8 ( P <0.0001 for both). LE gel 0.38% TID was safe and well tolerated, with only 1 LE-treated subject experiencing an IOP elevation ≥10 mm Hg. Most treatment-related AEs were mild and occurred less frequently with LE gel 0.38% than with vehicle. The majority (>75%) of subjects in each treatment group reported no drop discomfort. There were no reports of blurred vision with LE gel. Conclusion The results of this integrated analysis indicate that LE (submicron) gel 0.38% administered TID is safe and effective for the treatment of ocular inflammation and pain following cataract surgery, with minimal risk of IOP elevation.

Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38%: A Review in Post-Operative Inflammation and Pain Following Ocular Surgery

“…Loteprednol etabonate is a carbon-20 ester-based ophthalmic corticosteroid which binds to glucocorticoid receptors and inhibits the inflammatory response [ 15 , 16 ]. Loteprednol etabonate gel 0.38% retains the rheological and mucoadhesive properties of the previous 0.5% gel formulation but differs in drug particle size, drug concentration and formulation excipients [ 17 ]. Loteprednol etabonate particle size has been reduced in the submicron 0.38% gel, with the median particle diameter ranging between 0.4 and 0.6 µm (vs 3–5 µm in the micronized 0.5% gel) [ 15 , 17 ].…”

“…Loteprednol etabonate gel 0.38% retains the rheological and mucoadhesive properties of the previous 0.5% gel formulation but differs in drug particle size, drug concentration and formulation excipients [ 17 ]. Loteprednol etabonate particle size has been reduced in the submicron 0.38% gel, with the median particle diameter ranging between 0.4 and 0.6 µm (vs 3–5 µm in the micronized 0.5% gel) [ 15 , 17 ]. The smaller particle size results in a greater total surface area of loteprednol etabonate particles exposed to tears, leading to faster dissolution and improved penetration through the ocular surface [ 15 ].…”

“…The efficacy of loteprednol etabonate gel 0.38% in reducing post-operative inflammation and pain following cataract surgery was evaluated in two phase III randomized, parallel-group, double-masked, vehicle-controlled, multicentre trials that were conducted in the USA (hereafter referred to as Study A [ 18 ] and Study B [ 19 ]). Results of the individual trials and an analysis of integrated data [ 17 ] are available.…”

“…Patients ≥ 18 years of age were eligible in both studies if they had: undergone routine uncomplicated cataract surgery by phacoemulsification with posterior chamber intraocular lens implantation in one eye (not in combination with any other surgery); a potential post-operative pinhole Snellen corrected distance visual acuity of ≥ 20/200 in the operated eye; and ≥ grade 2 anterior chamber (AC) cells (6–15 cells) on the first post-operative day [ 17 – 19 ]. Patient exclusion criteria included: history or presence of generalized systemic disease or serious ocular conditions (including cystoid macular oedema, glaucoma and ocular hypertension); prior ocular surgery (≤ 3 months in the study eye or ≤ 2 weeks in the fellow eye) or glaucoma-related surgery; IOP ≥ 21 mm Hg at screening or baseline; or ocular or systemic therapy (e.g.…”

“…Patient exclusion criteria included: history or presence of generalized systemic disease or serious ocular conditions (including cystoid macular oedema, glaucoma and ocular hypertension); prior ocular surgery (≤ 3 months in the study eye or ≤ 2 weeks in the fellow eye) or glaucoma-related surgery; IOP ≥ 21 mm Hg at screening or baseline; or ocular or systemic therapy (e.g. NSAIDs, mast cell stabilisers, antihistamines, decongestants, corticosteroids, glucocorticoids or immunosuppressants) required 7–30 days before cataract surgery or during the 18 days post-surgery [ 17 – 19 ].…”