Reversal of Pharmacologic Mydriasis in Pediatric Subjects with Ryzumvi (0.75% Phentolamine Ophthalmic Solution): A Post-Hoc Pooled Analysis from Three Randomized, Placebo-Controlled Phase 3 Trials.

PURPOSE: To evaluate the safety and efficacy of 0.75% phentolamine ophthalmic solution (POS), a non-selective adrenergic antagonist, in reversing pharmacologically induced mydriasis in a post-hoc exploratory analysis of pediatric subjects aged 3-17 years.

METHODS

The 68 pediatric subjects included in this analysis were enrolled in one of three randomized, double-masked, controlled phase 3 clinical trials. Subjects received 1 or 2 drops of POS or placebo in each eye, administered 1 hour after pharmacologically induced mydriasis with 1% tropicamide, 2.5% phenylephrine, or Paremyd™ (0.25% tropicamide/1% hydroxyamphetamine). The fellow eye, which received a uniform single drop of study medication across all trials, was selected for this pooled efficacy analysis. The primary endpoint was the percentage of subjects returning to ≤0.2 mm of baseline photopic pupil diameter (PD) at 90 minutes. Secondary endpoints included return to ≤0.2 mm at additional time points, change in photopic PD from maximum dilation (0 minutes), time to return to baseline PD, and safety outcomes including adverse events (AEs) or serious AEs (SAEs).

RESULTS

At 90 minutes, 19/38 (50%) of POS-treated eyes and 4/30 (13%) of placebo-treated eyes returned to ≤0.2 mm of baseline PD. The greatest separation occurred at 3 hours, when 82% of POS-treated eyes and 20% of placebo-treated eyes achieved reversal. Mean time to recovery to ≤0.2 mm of baseline PD was more than 5 hours faster with POS. POS was well tolerated, with no SAEs or discontinuations. Treatment-related AEs in ≥5% of POS subjects consisted of mild, transient conjunctival hyperemia and instillation-site discomfort. No clinically meaningful changes in intraocular pressure, blood pressure, heart rate, or distance visual acuity were observed.

CONCLUSION

In this exploratory pooled analysis, POS appeared to accelerate the reversal of pharmacologically induced mydriasis in pediatric subjects and demonstrated an acceptable safety profile. Larger, prospectively powered pediatric studies are warranted.

TRIAL REGISTRATION: All three trials were registered with ClinicalTrials.gov (MIRA-2, NCT04620213; MIRA-3, NCT05134974; MIRA-4, NCT05223478).