Ripasudil-Brimonidine Fixed-Dose Combination vs Ripasudil or Brimonidine: Two Phase 3 Randomized Clinical Trials

PURPOSE: To confirm the superiority of the in-traocular pressure (IOP)-lowering effect of the ripasudil -brimonidine fixed-dose combination (RBFC, K-232) to ripasudil 0.4% or brimonidine 0.1% oph-thalmic solution.center dot DESIGN: Two prospective multicenter, randomized, double-or single-masked, active-controlled, phase 3 trials.center dot METHODS: Patients with primary open-angle glaucoma or ocular hypertension whose IOP level was >= 18 mm Hg during treatment with ripasudil or brimonidine alone were randomized to 2 groups (RBFC and ripasudil) in a 1:1 ratio in the ripasudil-controlled trial and to 3 groups (RBFC, brimonidine, and ripasudil-brimonidine combi-nation) in a 2:2:1 ratio in the brimonidine-controlled trial. The allocated study drugs were instilled twice daily for 8 weeks. The primary efficacy endpoint was the change in IOP 2 hours after instillation (11 AM) from the baseline to weeks 4, 6, and 8.center dot RESULTS: There were 206 patients randomized in the ripasudil-controlled trial. Changes in IOP were -2.6 and -1.2 mm Hg in the RBFC and ripasudil groups, respec-tively, with a difference of -1.4 mm Hg (95% CI = -1.8 to -1.0 mm Hg; P < .001). There were 282 randomized patients in the brimonidine-controlled trial. Changes in IOP were -3.4 and -1.5 mm Hg in the RBFC and bri-monidine groups, respectively, with a difference of -1.8 mm Hg (95% CI = -2.3 to -1.4 mm Hg; P < .001). The most frequent adverse event was conjunctival hyper-emia. CONCLUSIONS: The IOP-lowering effect of RBFC was superior to that of ripasudil or brimonidine. (Am J Ophthalmol 2023;248: 35-44. (c) 2022 Published by El-sevier Inc.)