PURPOSE: Brimonidine tartrate ophthalmic solution (0.025%; BTOS) contains benzalkonium chloride (BAK), the most used preservative in ophthalmic pharmaceuticals. Exposure of the ocular surface to BAK can induce/exacerbate irritation. A preservative-free formulation of BTOS (BTOS-PF) has been developed and the two formulations are evaluated in this study.

METHODS: This was a multicenter, double-masked, randomized, active-controlled, parallel-group study in healthy adults (>18 years) with ocular redness, conducted at 6 US sites. The study occurred over 5 weeks out to Visit 4 (Day 36 + 1 day). After the initial in-office dose at Visit 1, 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) at Visit 1.

RESULTS: 380 participants were randomized 1:1 to receive BTOS-PF or BTOS and formed the ITT population. 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 (TEAEs) were reported by 37/188 (19.7%) subjects in the BTOS-PF group and 61 TEAEs reported by 39/190 (20.5%) subjects in the BTOS group.

CONCLUSION: 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 favourable and similar to that of BTOS.