Phentolamine mesylate ophthalmic solution provides long lasting pupil modulation and improves visual acuity

Abstract

Purpose : Phentolamine mesylate ophthalmic solution (PM) was previously shown to have short term beneficial effects in the eye (≥ 2 hours), including intra ocular pressure (IOP) lowering, pupil diameter (PD) decrease, and increase of visual acuity and contrast sensitivity, while causing mild to moderate conjunctival hyperemia. This study evaluates the chronic safety and efficacy of 1% PM once-a-day evening dose in the presbyopic population.

Methods : In this randomized, double-masked, placebo-controlled, multiple dose Phase 2b study in 39 subjects (mean age = 60 yrs, IOP ≥ 22 and ≤30 mmHg), we evaluated the dosing regimen, safety, vision performance and IOP efficacy following once daily evening 1% PM dosing for 14 days. The key endpoints were the mean change in diurnal IOP, PD, distance corrected near visual acuity (DCNVA) and conjunctival hyperemia at day 8 and 15. Analysis of covariates (ANCOVA) was performed to assess statistical significance between treatment groups for each parameter.

Results : 1% PM in the evening led to a -2.30 mmHg day 15 mean diurnal IOP change from baseline compared to a -2.18 mmHg change for placebo (p=0.894). There was a trend toward greater IOP lowering in subjects with lower IOP baselines (-3.57 mmHg for PM compared to +3.10 mmHg for placebo, p=0.0489, at baseline IOP < 22 mmHg). PM led to -20.2% and -20.0% mean change in PD at Day 8 and Day 15 compared to -1.5% and +1.9% for placebo in photopic conditions (p<0.0001), with similar results in mesopic conditions. PD reduction for PM was sustained through 36 hours post-dose at Day 16 (-20.6% compared to +6.0%, p<0.0001). Further, more patients with PM showed at least 1 line of improvement in DCNVA at Day 15 (63.2% compared to 20.0%, p=0.0259), with a trend for 2- and 3-lines at all days. There was no conjunctival hyperemia difference between the two groups at 8am on day 15 (p=0.3476), no burning, ptosis, tachyphylaxis, rebound or other AEs/SAEs.

Conclusions : 1% PM is well tolerated in the eye and the evening dose regimen minimizes eye redness during daytime while benefiting near visual acuity in the presbyopic population. The sustained (36 hour) pupil modulation and visual acuity effect data suggest that PM is a good candidate for remediating photic phenomena and night vision disturbances (NVD). Follow up clinical trials shall investigate the effect of 1% PM in patients with NVD

This is a 2020 ARVO Annual Meeting abstract.