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

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.

Keywords: cataract surgery; integrated analysis; loteprednol etabonate; postoperative inflammation; postoperative pain; submicron.

Conflict of interest statement

MEC, HHD, and JLV are employees of Bausch Health US, LLC. The authors report no other conflicts of interest in this work.

Figures

Figure 1

Participant flow. Notes:aBased on the intent-to-treat population. Reasons for discontinuations are primary reasons for withdrawal from the intent-to-treat population. Abbreviation: LE, loteprednol etabonate; TID, three times daily.

Figure 2

Percentage of subjects with complete resolution of AC cells and grade 0 pain at day 8 (visit 5) in the ITT population. Note:aPearson Chi-squared test P<0.0001 vs vehicle. Abbreviations: AC, anterior chamber; ITT, intent-to-treat; LE, loteprednol etabonate; TID, three times daily.

Figure 3

(A) Mean (SD) change from baseline in anterior chamber cells (ITT population). (B) Mean (SD) change from baseline in anterior chamber flare (ITT population). (C) Mean (SD) change from baseline in anterior chamber cells and flare combined (ITT population). Notes:aP<0.01 vs vehicle; bP<0.0001 vs vehicle. Negative values denote improvement. Missing values and post-rescue values were imputed using LOCF, and data were analyzed using a Cochran-Mantel-Haenszel mean score test. Abbreviations: LE, loteprednol etabonate; ITT, intent-to-treat; LOCF, last observation carried forward; TID, three times daily.