Submicron loteprednol etabonate ophthalmic gel 0.38% for the treatment of inflammation and pain after cataract surgery

Fong, Raymond; Silverstein, Bruce E.; Peace, James; Williams, Jon I.; Vittitow, Jason L

doi:10.1016/j.jcrs.2018.06.056

Cited by 9 publications

(29 citation statements)

References 8 publications

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“…The clinical development program designed to evaluate the safety and efficacy of LE (submicron) gel 0.38% included two similarly designed, Phase III, randomized, vehicle-controlled trials20,21 of LE gel 0.38% or vehicle instilled either BID or TID, for the treatment of postoperative inflammation and pain following cataract surgery with intraocular lens implantation. In both studies, LE gel 0.38% administered TID was safe and effective in the treatment of ocular inflammation and pain following cataract surgery, leading to the United States FDA approval of this new LE (submicron) gel formulation with TID dosing in February 2019 with the brand name of Lotemax ® SM 18.…”

Section: Introductionmentioning

confidence: 99%

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

Fong

Cavet²,

DeCory³

et al. 2019

OPTH

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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.

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Section: Introductionmentioning

confidence: 99%

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

Fong

Cavet²,

DeCory³

et al. 2019

OPTH

Self Cite

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“…Indeed, 2 pivotal Phase 3, randomized, multicenter, vehicle-controlled clinical trials have demonstrated that LE (submicron) gel 0.38% appeared safe and effective for the reduction of inflammation and pain postcataract surgery, with a TID dosing regimen. 47,54 In both studies, the numbers of subjects with complete resolution of ocular pain and anterior chamber cells (primary efficacy endpoint) were significantly higher in the LE (submicron) gel 0.38% TID dosing group compared to the vehicle group. Improvements in resolution of inflammation and pain postcataract surgery were also observed with BID dosing, despite the drug not meeting the primary efficacy endpoint in 1 study.…”

Section: Discussionmentioning

confidence: 98%

“…In support of the latter, there were no reports of drug-related blurred vision, and most subjects reported no discomfort upon instillation in a Phase 3 study evaluating LE gel 0.38% for treatment of postsurgical inflammation and pain. 47…”

Section: Discussionmentioning

confidence: 99%

“…Improvements in resolution of inflammation and pain postcataract surgery were also observed with BID dosing, despite the drug not meeting the primary efficacy endpoint in 1 study. 47,54 In addition, there was minimal impact on IOP, with a total of only 4 reports of IOP elevation ≥10 mm Hg in the LE (submicron) gel 0.38% BID and TID treatment groups across both studies encompassing a total of 742 LE-treated subjects. 47,54…”

Section: Discussionmentioning

confidence: 99%

“…47,54 In addition, there was minimal impact on IOP, with a total of only 4 reports of IOP elevation ≥10 mm Hg in the LE (submicron) gel 0.38% BID and TID treatment groups across both studies encompassing a total of 742 LE-treated subjects. 47,54…”

Section: Discussionmentioning

confidence: 99%

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Rheological Properties, Dissolution Kinetics, and Ocular Pharmacokinetics of Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38%

Cavet¹,

Glogowski²,

Lowe

et al. 2019

Journal of Ocular Pharmacology and Therapeutics

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Purpose: To evaluate rheological properties, in vitro dissolution, and in vivo ocular pharmacokinetics of loteprednol etabonate (LE) (submicron) ophthalmic gel 0.38%. Methods: The viscosity of the LE gel 0.38% formulation was measured with a controlled stress rheometer. Dissolution kinetics were evaluated in a fixed-volume and flow-through assay. Rabbits received a single instillation of LE (submicron) gel 0.38% (both eyes), and concentrations of LE in ocular tissues were determined through 24 h by liquid chromatography with tandem mass spectrometry. Where indicated, comparators included micronized LE gel 0.38%, 0.5% (Lotemax ® gel), and 0.75%. Results: LE (submicron) gel 0.38% exhibited shear-thinning characteristics similar to LE gel 0.5% with nearly identical yield stress. LE (submicron) gel 0.38% released 2.6-fold more LE into the dissolution medium than micronized LE gel 0.5% over 30 s in the fixed-volume dissolution assay, and submicron LE attained higher concentrations of dissolved LE than micronized LE gel 0.38% in the flow-through dissolution assay. In rabbits, the maximal concentration and area-under-the-curve over 24 h for LE in aqueous humor were 2.5- and 1.8-fold higher, respectively, for LE (submicron) gel 0.38% versus micronized LE gel 0.5% (both P < 0.001). Pharmacokinetic parameters were similar for most other tissues. Conclusions: LE (submicron) gel 0.38% demonstrated similar rheological properties to micronized LE gel 0.5% but faster dissolution, thus providing similar or higher LE concentrations in the aqueous humor, cornea, and iris-ciliary body after ocular dosing in rabbits despite a lowered concentration of drug in the formulation.

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Dose Uniformity of Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38% Compared with Prednisolone Acetate Ophthalmic Suspension 1%

Marlowe¹,

Cavet²,

Coffey³

2021

Ophthalmol Ther

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Introduction: Loteprednol etabonate (submicron) ophthalmic gel 0.38% (LE SM gel 0.38%) is a corticosteroid formulation designed to retain the nonsettling characteristics of loteprednol etabonate ophthalmic gel 0.5%, but with reduced drug particle size to improve ocular penetration, allowing for reduced dosing frequency. This study compared the dose uniformity of LE SM gel 0.38% with branded and generic prednisolone acetate (PA) 1% suspensions under simulated in-use dosing conditions. Methods: Drug concentrations in drops of LE SM gel 0.38% and PA 1% suspensions, expressed from bottles that were shaken or not shaken, were determined during 2 weeks of simulated on-label dosing (LE SM gel 0.38%: three times daily; PA suspensions: four times daily). Sedimentation of drug particles was assessed for each product using dispersion analysis. Results: The mean (SD) percent declared drug concentration of LE SM gel 0.38% over 2 weeks was 103.2% (1.3%) when the drug was dispensed from shaken bottles and 103.3% (1.5%) when dispensed from unshaken bottles. However, for branded and generic PA suspensions, mean (SD) percent declared concentrations were 102.2% (1.4%) and 98.3% (2.9%), respectively, when dispensed from shaken bottles; and 89.2% (18.6%) and 78.3% (13.5%), respectively, when dispensed from unshaken bottles. Dispersion analysis showed that drug particles in LE SM gel 0.38% remained fully suspended under accelerated sedimentation conditions, whereas both branded and generic PA suspension drug particles settled out of suspension. Conclusions: LE SM gel 0.38% delivered the drug consistently at the declared concentration over the entire 2 weeks of simulated in-use dosing conditions, regardless of whether the drug was dispensed from shaken or unshaken bottles. However, both branded and generic PA suspensions required the bottle to be shaken to provide a consistent drug concentration.

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Submicron loteprednol etabonate ophthalmic gel 0.38% for the treatment of inflammation and pain after cataract surgery

Abstract: In this study, submicron loteprednol etabonate gel 0.38% appeared safe and effective in the treatment of postoperative inflammation and pain whether instilled 2 times or 3 times a day.

Cited by 9 publications

References 8 publications

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

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

Rheological Properties, Dissolution Kinetics, and Ocular Pharmacokinetics of Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38%

Dose Uniformity of Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38% Compared with Prednisolone Acetate Ophthalmic Suspension 1%

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