PURPOSE: This study evaluated the efficacy and safety of a novel brimonidine tartrate ophthalmic solution 0.025% formulated with sodium hyaluronate (BTOS-HA) against the original brimonidine tartrate ophthalmic solution 0.025% (BTOS) in the treatment of ocular redness.

METHODS: In this multicenter, double-masked, Phase 3 trial, adults with baseline ocular redness >1 (0–4 scale) in both eyes were randomized 1:1 to BTOS-HA or BTOS. Both were dosed QID for 4 weeks. The primary endpoint was investigator-graded ocular redness during Day 1 over 8 timepoints (5–240 minutes) after instillation. Noninferiority required the upper bound of the 95% CI for the mean difference between treatments to remain ≤0.22 units at all 8 timepoints. Key secondary endpoints included mean changes in pre-instillation ocular redness score at 1 and 480 minutes. Safety assessments included TEAEs, BCVA, slit-lamp findings, IOP, dilated fundus exam, and rebound redness assessed out to Day 36.

RESULTS: A total of 578 subjects were randomized (289 in each group). BTOS-HA was statistically noninferior to BTOS at all 8 primary post-instillation time points (5–240 minutes), with all upper confidence limits ≤0.22. At the pre-specified secondary time points, BTOS-HA was noninferior at 1 minute, 360 minutes, and 480 minutes. Additionally, rapid onset within 30 seconds and redness reduction through 10 hours relative to baseline was demonstrated. Safety outcomes were comparable. TEAEs were infrequent and similar between groups. In the BTOS-HA group, only instillation-site irritation (1.7%) and urinary tract infection (1.0%) occurred in ≥1% of subjects; all ocular TEAEs were mild or moderate. Serious TEAEs were rare (BTOS-HA n=1; BTOS n=2), and not related to treatment. Rebound redness was low (BTOS-HA 2.2%; BTOS 1.1%). No clinically meaningful differences were observed in BCVA, IOP, slit-lamp biomicroscopy, or dilated fundus exam in either group.

CONCLUSIONS: BTOS-HA demonstrated noninferiority to original BTOS across all primary and key secondary time points. Relative to baseline, BTOS-HA demonstrated rapid onset within 30 seconds and sustained redness reduction up to 10 hours. The novel BTOS-HA formulation was well tolerated with a safety profile comparable to the well-established safety of BTOS and low rates of rebound redness. These findings support BTOS-HA as an effective redness-relief formulation.