Treatment With 0.75% Phentolamine Ophthalmic Solution Reverses Mydriasis In Healthy Subjects: Results From Mira-2 And Mira-3, Pivotal Phase 3 Clinical Trials

The MIRA-2 and MIRA-3 trials evaluated the safety, tolerability, and efficacy of 0.75% Phentolamine Ophthalmic Solution (POS) in reversing pharmacologically induced mydriasis in normal healthy subjects. A total of 553 subjects, including 45 pediatric subjects aged 12-17 years, were randomized to receive POS or placebo following dilation with a mydriatic agent. Stratification by light or dark irides was 1:1, and treatment was administered to both eyes with the study eye defined as the right eye. The purpose of this abstract is to present the primary endpoint results and safety data of these trials.

MIRA-2 (NCT04620213) was a randomized, placebo-controlled, double-masked Phase 3 trial evaluating the safety and efficacy of POS in pharmacologically-induced mydriasis conducted at 12 investigational sites in the United States.

MIRA-3 (NCT05134974) was a randomized, placebo-controlled, double-masked Phase 3 trial evaluating the safety and efficacy of POS in pharmacologically-induced mydriasis conducted at 16 investigational sites in the United States.

A total of 185 and 368 subjects were enrolled in MIRA-2 and MIRA-3, respectively, including pediatric subjects aged 12-17 years. Subjects were randomized 1:1 or 2:1 to receive POS or placebo, respectively, administered to both eyes following mydriatic drug administration. The primary efficacy endpoint was the percent of study eyes with reversal of mydriasis 90 minutes post-dose, with a pupil diameter (PD) threshold of ≤0.2 mm from baseline. Safety assessments were conducted throughout the trials, including monitoring of adverse events (AEs) and assessments of vital signs, clinical laboratory tests, and ocular assessments.

In both trials, POS significantly increased the percentage of study eyes returning to ≤0.2 mm from baseline PD compared to placebo at 90 minutes post-dose (49% vs 7% in MIRA-2, 58% vs 6% in MIRA-3, both p<0.0001) and 60 minutes post-dose (28% vs 2% in MIRA-2, 42% vs 2% in MIRA-3, both p<0.0001). Similar results were observed at all other time points, persisting through 24 hours. POS also significantly reduced mean PD from maximum PD at 60 minutes post-dose, with a reduction of 20-30% compared to placebo. AEs were primarily ocular and mild in intensity, with no serious AEs reported. Vital signs, clinical laboratory tests, and ocular assessments were within normal limits and showed no clinically significant differences between arms.

POS was safe and well-tolerated with rapid reversal of mydriasis upon treatment. These results support the use of POS as a reversal drop following use of mydriatic agent for comprehensive eye exams, procedures, and surgeries. An NDA submission for POS eye drops is under review by the United States FDA.