A Randomized Phase 2 Trial Comparing Omidenepag Isopropyl 0.002% Once and Twice Daily in Subjects With Primary Open-angle Glaucoma or Ocular Hypertension (SPECTRUM-6).

PRCIS: No significant difference was found between the intraocular pressure (IOP) lowering of omidenepag isopropyl 0.002% once daily (QD) and twice daily (BID). However, adverse events (AEs) were higher in the BID arm; thus, QD dosing is the preferred dosing frequency for further investigation. PURPOSE: This phase 2, randomized, double-masked, parallel-arm, multicenter study (NCT03858894) was conducted in the United States to examine whether the efficacy and safety of omidenepag isopropyl 0.002% BID dosing was superior to QD dosing in subjects with primary open-angle glaucoma or ocular hypertension. METHODS: Randomized subjects (1:1) received omidenepag isopropyl 0.002% QD (n=50) or BID (n=48) for 6 weeks (after a ≤4-week washout period). IOP was measured at 8:00 am, 12:00 pm, and 4:00 pm at baseline and weeks 2 and 6. The primary efficacy endpoint was IOP at each timepoint at weeks 2 and 6. AEs were evaluated. RESULTS: Baseline mean diurnal IOP (±SD) post washout was 25.4±2.9 mm Hg (BID) and 24.6±1.9 mm Hg (QD). At weeks 2 and 6, clinically significant IOP reductions from baseline were observed for omidenepag isopropyl BID and QD treatments. Least-squares mean (±SE) IOP differences (BID versus QD) were not statistically significant (week 2: 0.44±0.68 to 1.08±0.65 mm Hg; week 6: 0.36±0.63 to 0.68±0.68 mm Hg) at any timepoint (all P > 0.05). AEs were 3-fold greater in the BID arm (41.7%; QD: 14.0%); the most frequently reported AE was conjunctival/ocular hyperemia (BID: 22.9%; QD: 2.0%). Five subjects discontinued omidenepag isopropyl prematurely, 4 of 5 owing to AEs (BID: 4; QD: 0). CONCLUSION: In this study, the benefit-risk profile of omidenepag isopropyl 0.002% QD was more favorable than the benefit-risk profile of BID. This difference was driven by a higher incidence of local tolerability issues in the BID arm.

Phentolamine Mesylate Ophthalmic Solution Provides Lasting Pupil Modulation and Improves Near Visual Acuity in Presbyopic Glaucoma Patients in a Randomized Phase 2b Clinical Trial.

PURPOSE: Phentolamine mesylate ophthalmic solution (PMOS), applied to the eye topically, was shown previously to have beneficial effects in patients with dim light vision disturbances (DLD), including decreased pupil diameter (PD), improved best-corrected distance visual acuity (BCDVA), as well as lower intraocular pressure (IOP). The ORION-1 trial evaluated the long-term safety and efficacy of PMOS in a glaucomatous, presbyopic population. PATIENTS AND METHODS: In this randomized, double-masked, multi-center, placebo-controlled, multiple-dose Phase 2b trial, 39 patients with elevated IOP were randomized to receive one evening dose of study medication or placebo for 14 days. The primary outcome measure was mean change in diurnal IOP, and the key secondary outcome measures included changes in PD, distance-corrected near visual acuity (DCNVA), and conjunctival hyperemia. RESULTS: Use of 1% PMOS did not lead to a statistically significant decrease in diurnal IOP compared to placebo (P = 0.89) but trended toward a greater decrease in patients with lower IOP baselines. PMOS produced a statistically significant mean 20% PD reduction under both photopic and mesopic conditions that was sustained for 36 hours post-dosing. A statistically significant number of patients with PMOS compared to placebo demonstrated ≥1 line of improvement in photopic DCNVA at day 8 (P = 0.0018), day 15 (P = 0.0072), and day 16 (P = 0.0163), with a trend for 2- and 3-line improvements at all time points. There was no statistical difference in conjunctival hyperemia compared to placebo. CONCLUSION: Although mean IOP was not lowered significantly, daily evening dosing of 1% PMOS was found to be well tolerated with no daytime conjunctival redness and demonstrated improvement in DCNVA with sustained PD reduction in a glaucomatous and presbyopic population. Smaller pupil size can have beneficial effects in improving symptoms of presbyopia and DLD, which will be the focus of further studies.