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

by Selleckchem | Jul 10 2023

Purpose: To confirm the superiority of the intraocular pressure (IOP)-lowering effect of the ripasudil-brimonidine fixed-dose combination (RBFC, K-232) to ripasudil 0.4% or brimonidine 0.1% ophthalmic solution.

Design: Two prospective multicenter, randomized, double- or single-masked, active-controlled, phase 3 trials.

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 combination) 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.

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, respectively, 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 brimonidine 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 hyperemia.

Conclusions: The IOP-lowering effect of RBFC was superior to that of ripasudil or brimonidine.

Comments:

The purpose of the study was to confirm the superiority of the ripasudil-brimonidine fixed-dose combination (RBFC, K-232) in lowering intraocular pressure (IOP) compared to ripasudil 0.4% or brimonidine 0.1% ophthalmic solution. The study design involved two prospective multicenter, randomized, double- or single-masked, active-controlled, phase 3 trials.

The study included patients with primary open-angle glaucoma or ocular hypertension who had an IOP level of ≥18 mm Hg while being treated with either ripasudil or brimonidine alone. In the ripasudil-controlled trial, patients were randomized to two groups: RBFC and ripasudil, in a 1:1 ratio. In the brimonidine-controlled trial, patients were randomized to three groups: RBFC, brimonidine, and the ripasudil-brimonidine combination, in a 2:2:1 ratio. The study drugs were administered twice daily for 8 weeks. The primary efficacy endpoint was the change in IOP 2 hours after instillation (11 AM) from baseline to weeks 4, 6, and 8.

The results of the ripasudil-controlled trial showed that the change in IOP was -2.6 mm Hg in the RBFC group and -1.2 mm Hg in the ripasudil group, with a difference of -1.4 mm Hg (95% CI = -1.8 to -1.0 mm Hg; P < .001). In the brimonidine-controlled trial, the change in IOP was -3.4 mm Hg in the RBFC group and -1.5 mm Hg in the brimonidine group, with a difference of -1.8 mm Hg (95% CI = -2.3 to -1.4 mm Hg; P < .001). The most common adverse event reported was conjunctival hyperemia.

In conclusion, the study found that the IOP-lowering effect of the ripasudil-brimonidine fixed-dose combination (RBFC) was superior to that of ripasudil or brimonidine alone.