Global eye health company Bausch + Lomb last week announced results of a Phase 3 trial, published in the Journal of Cataract and Refractive Surgery (JCRS). The multicenter, double-masked, vehicle-controlled, randomized, parallel-group study evaluated the clinical safety and efficacy of submicron loteprednol etabonate ophthalmic gel, 0.38%.
This investigational formulation of loteprednol etabonate has a reduced concentration and reduced dosing frequency over existing loteprednol etabonate formulations. The study found the new formulation to meet the primary efficacy endpoints in that it was significantly more effective than vehicle in completely resolving ocular inflammation and pain following cataract surgery. Additionally, the results showed that submicron loteprednol etabonate ophthalmic gel, 0.38% had an acceptable safety profile regardless of whether it was administered two or three times per day.
The Phase 3 study was conducted at 45 ophthalmology practices in the United States and enrolled 514 patients age 18 years or older who had anterior chamber cells grade 2 or higher (6 to 15 cells) the day after uncomplicated cataract surgery. Study participants were randomized to one of four treatment groups (submicron loteprednol etabonate ophthalmic gel, 0.38% twice daily, submicron loteprednol etabonate ophthalmic gel, 0.38% three times daily, vehicle gel twice daily, or vehicle gel three times daily) for 14 days. The primary efficacy endpoints were the proportion of patients with complete resolution of anterior chamber cells (defined as a grade of 0 [or no cells]), a marker of ocular inflammation, and the proportion of patients with grade 0 pain (no pain) at postoperative day 8 in the submicron loteprednol etabonate ophthalmic gel, 0.38% twice daily, submicron loteprednol etabonate ophthalmic gel, 0.38% three times daily, and the combined vehicle groups. Safety and tolerability endpoints included ocular symptoms other than pain (e.g., itching, tearing, and discharge), study drug sensation, the incidence of ocular and non-ocular adverse events, and ocular signs (biomicroscopy), among others. Study participants who experienced worsening or no change in inflammation could be placed on anti-inflammatory rescue medication at any time during the trial.
Findings showed that a significantly greater proportion of patients who received submicron loteprednol etabonate ophthalmic gel, 0.38% dosed twice daily or three times daily had complete resolution of anterior chamber cells on postoperative day 8 (26.9 percent and 28.7 percent, respectively) compared with the vehicle group (9.3 percent; p<0.0001). Similarly, a significantly greater proportion of patients who received submicron loteprednol etabonate ophthalmic gel, 0.38% twice daily or three times daily had no ocular pain (grade 0) on day 8 (73.7 percent and 73.1 percent, respectively) compared with the vehicle group (47.7 percent; p<0.001). For patients in the submicron loteprednol etabonate ophthalmic gel, 0.38% group, statistically significant differences in both anterior chamber cells and ocular pain were sustained at all subsequent visits (through postoperative day 18) relative to vehicle. Additionally, significantly fewer patients in the submicron loteprednol etabonate ophthalmic gel, 0.38% twice daily group and three times daily group (14.0 percent and 11.1 percent, respectively) required rescue medication by day 8 compared with those in the vehicle group (41.9 percent; p<0.0001). The most common ocular adverse events were eye pain, photophobia (extreme sensitivity to light), and foreign body sensation.
The U.S. Food and Drug Administration has accepted the New Drug Application for submicron loteprednol etabonate ophthalmic gel, 0.38% with a Prescription Drug User Fee Act (PDUFA) action date of Feb. 25, 2019.
Read the full press release from Bausch + Lomb.