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)

Abstract

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.