Abstract
Purpose :
Pharmacologically induced mydriasis, a key aspect of comprehensive eye exams and procedures, can lead to photophobia, discomfort, and impairment of vision. The MIRA-2 and MIRA-3 trials assessed time savings of reversing pharmacologically induced mydriasis with 0.75% phentolamine ophthalmic solution (POS).
Methods :
MIRA-2 and MIRA-3 were multi-center, randomized, placebo-controlled, double-masked clinical trials in healthy subjects (approximately n=553; age ≥12 years). Stratified by iris color, subjects were randomized to mydriatic agent 3:1:1 (2.5% phenylephrine, 1% tropicamide, or Paremyd, respectively) and POS or placebo treatment 1:1 in MIRA-2 and 2:1 in MIRA-3. The primary efficacy endpoint was the percent of subjects returning to ≤ 0.2 mm from baseline photopic pupil diameter (PD) at 90 minutes (min). A series of endpoints were evaluated in a prespecified hierarchical analysis for the integrated dataset, including time to return to baseline PD.
Results :
Across MIRA-2 and MIRA-3, 338 subjects received POS (mean age 33 years, 60% female) and 215 subjects received placebo (mean age 33 years, 62% female). In addition, time to reversal of mydriasis for both study and fellow eyes overall, for each mydriatic agent, and for light and dark irides were endpoints that met statistical significance in the hierarchy. Overall, eyes treated with POS showed a significantly faster mean time to return to ≤ 0.2 mm from baseline PD compared with placebo, for study eyes and fellow eyes (2.2 vs 6.1 hr, 2.6 vs 6.3 hr, respectively; p<0.0001). Results for subjects receiving phenylephrine, tropicamide, or Paremyd were similar (1.3 vs 5.2 hr, 3.9 vs 7.6 hr, 3.0 vs 7.2 hr respectively; p<0.0001) as well as subjects with light or dark irides (1.9 vs 6.7 hr, 2.4 vs 5.5 hr respectively; p<0.0001).
Conclusions :
MIRA-2 and MIRA-3 represent two well-controlled and confirmatory Phase 3 clinical trials where the primary and secondary endpoints met clinical and statistical significance. With POS, a time savings of approximately 4 hours was seen regardless of dilating agent or iris color. Based on its efficacy and favorable safety and tolerability profile, an NDA for POS has been submitted for consideration of regulatory approval for the treatment of pharmacologically-induced mydriasis
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.