A Multicenter Randomized Double-Masked Study Comparing Preservative-free Brimonidine Tartrate Ophthalmic Solution 0.025% with LUMIFY® 0.025% for Ocular Redness in Adults

Abstract

Introduction: Ocular redness is common, can affect quality of life, and can be relieved by short-term use of topical adrenergic receptor (AR) agonists. Brimonidine tartrate ophthalmic solution 0.025% (LUMIFY^® 0.025%) is the first α2-AR-selective agonist approved for ocular redness. The preservative benzalkonium chloride (BAK) maintains ophthalmic solution sterility, reducing the risk of ocular infections, but may cause symptoms of ocular surface disease (OSD) in some patients. A BAK-free formulation of LUMIFY 0.025% (BTOS-PF 0.025%) could offer a solution for BAK-sensitive patients.

Methods: This randomized, active-controlled, multicenter study aimed to establish non-inferior efficacy of BTOS-PF 0.025% to LUMIFY 0.025% and compare safety. Randomized participants received either formulation instilled as a single drop four times daily, for 4 weeks. The primary endpoint was investigator-assessed ocular redness at 5, 15, 30, 60, 90, 120, 180, and 240 min post-instillation at visit 1 (day 1). Eight hierarchical secondary endpoints included additional post-instillation timepoints at visit 1 and visits 2 and 3 (days 14 and 28), and participant-assessed redness.

Results: BTOS-PF 0.025% was statistically non-inferior to LUMIFY 0.025% for ocular redness reduction across the eight timepoints at visit 1. Efficacy for both formulations was seen as early as 1 min and up to 8 h post-instillation. BTOS-PF 0.025% performed similarly to LUMIFY 0.025% after 14 and 28 days, rebound redness rates were low and similar, and total clearance of ocular redness and participant-evaluated redness were similar. The safety profile of both formulations was similar, with no severe or serious ocular events.

Conclusions: BTOS-PF 0.025% was non-inferior to LUMIFY 0.025% in reducing ocular redness in adults, was well-tolerated, and offers an alternative topical solution, without loss of efficacy or compromised safety, for patients who prefer a preservative-free formulation or are at increased risk of OSD.

Clinical trial registration: ClinicalTrials.gov identifier: NCT05360784. Date of registration: 29 April 2022.

Keywords: Benzalkonium chloride; Brimonidine; Brimonidine tartrate ophthalmic solution 0.025%; Hyperemia; LUMIFY; Ocular redness; Patient preference; Preservative-free; Vasoconstriction.

Fig. 1

Participant disposition. *The ITT population included all randomized participants; the PPP population included participants in the ITT who did not have significant protocol deviations likely to affect the primary endpoint analysis; and the SPP population included participants in the ITT who did not have significant protocol deviations likely to affect the secondary endpoints and analyses. ^†The safety population included all randomized participants who received at least one dose of study drug. ^‡For each visit, a participant who had a pre-dose and a post-dose measure for the primary endpoint was defined to have completed the visit. AE adverse event, BTOS-PF brimonidine tartrate ophthalmic solution, preservative free, ITT intent-to-treat, PPP primary per-protocol, SPP secondary per-protocol

Fig. 2

A Change in mean ocular redness score from pre-instillation at visit 1. B Mean difference in ocular redness score between BTOS-PF 0.025% and LUMIFY 0.025% at visit 1. A Ocular redness was graded by the investigator on a scale from 0 to 4 in half-unit increments, where 0 corresponds to no redness and 4 corresponds to extremely severe redness. Error bars indicate the standard error of the mean score; missing data due to lack of efficacy or AEs were imputed using worst observation carried forward method (MNAR assumption). B Mean difference in investigator-assessed ocular redness score was assessed using a two-sample t test to compare BTOS-PF 0.025% (n = 190) and LUMIFY 0.025% (n = 190) using multiple imputation methodology (ITT population). Error bars indicate the two-sided 95% CI, with the dotted line indicating the pre-determined non-inferiority limit of 0.22; the table states the upper and lower 95% CI values for each timepoint, with bold numbers highlighting upper-limit values less than 0.22; and gray shading indicates timepoints that were analyzed for statistical non-inferiority as part of the primary endpoint analysis. AE adverse event, BTOS-PF brimonidine tartrate ophthalmic solution, preservative free, CI confidence interval, ITT intent-to-treat, MNAR missing not at random

Fig. 3

Change in mean ocular redness score at 1 min and 5 min from pre-instillation. Ocular redness was graded by the investigator on a scale from 0 to 4 in half-unit increments, where 0 corresponds to no redness and 4 corresponds to extremely severe redness. Missing data due to lack of efficacy or AEs were imputed using worst observation carried forward method (MNAR assumption). Error bars indicate the standard error of the mean score. AE adverse event, BTOS-PF brimonidine tartrate ophthalmic solution, preservative free, MNAR missing not at random