PURPOSE: Low-dose (0.025%) brimonidine tartrate ophthalmic solution (BTOS) is approved for the treatment of conjunctival hyperemia. As frequent exposure of the ocular surface to the preservative benzalkonium chloride can induce or exacerbate existing ocular irritation, a preservative-free formulation, BTOS-PF, has been developed. This study evaluated the efficacy and safety of BTOS-PF vs BTOS.

METHODS: This was a multicenter, double-masked, randomized, active-controlled, parallel-group study in healthy adults (>18 years) with ocular redness, conducted at six sites in the US. The study occurred over 5 weeks. After an initial in-office dose, both agents were self-administered 4 times daily ~4 hours apart for a duration of 4 weeks. The primary efficacy endpoint was ocular redness score as evaluated by the investigator prior to and at 5(+1), 15(+1), 30(+1), 60(+10), 90(+10), 120(+15), 180(+15), and 240(+15) minutes after investigational drug instillation (0–4-unit scale, allowing half-unit increments). Safety variables included physical exam including vital signs, adverse events (reported, elicited, and observed), best-corrected visual acuity at distance, slit lamp biomicroscopy, intraocular pressure, dilated ophthalmoscopy, and ocular rebound.

RESULTS: 380 participants were randomized 1:1. Baseline (pre-instillation) ocular redness values were comparable between the BTOS-PF and BTOS groups. All post-instillation redness values observed at all timepoints were also comparable between treatment arms, with mean differences between treatment groups ranging from -0.09 to 0.01 units, with upper confidence limits at all timepoints falling within the pre-determined limit for non-inferiority of 0.22 units. A total of 48 treatment-emergent adverse events were reported by 37/188 (19.7%) subjects in the BTOS-PF group and 61 treatment-emergent adverse events reported by 39/190 (20.5%) subjects in the BTOS group. The majority were mild. Tolerability, as measured by drop comfort assessment and questionnaire, was comparable between groups.

CONCLUSIONS: The primary endpoint was met with the novel BTOS-PF demonstrating statistical non-inferiority to BTOS in the reduction of ocular redness at all timepoints from 5 minutes to 240 minutes post-instillation. Overall, the safety profile of BTOS-PF was favorable and similar to BTOS.