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.

Fixed combination of latanoprost and timolol vs individual components for primary open-angle glaucoma or ocular hypertension: a randomized, double-masked study.

OBJECTIVE: To assess the efficacy and safety of fixed-combination latanoprost-timolol (FCLT) vs latanoprost or timolol monotherapy. METHODS: This 12-week, randomized, double-masked, parallel-group study included patients with open-angle glaucoma or ocular hypertension treated with a beta-blocker and with baseline intraocular pressure (IOP) of 26 through 36 mm Hg. Following washout, eligible patients were randomized to once-daily FCLT in the evening, latanoprost in the evening, or timolol in the morning. MAIN OUTCOME MEASURES: Postbaseline IOP assessments at 8 am, 10 am, and 4 pm at weeks 2, 6, and 12; statistical superiority of FCLT for the 18 pairwise comparisons between FCLT and the 2 monotherapies, using analysis of variance. RESULTS: All therapies resulted in significant IOP reductions from baseline. Pairwise comparisons favored FCLT at all time points. When the 18 comparisons were tested simultaneously, FCLT was statistically superior to latanoprost at 7 of 9 time points and at all 9 time points when compared with timolol. In addition, FCLT was associated with greater percentage reductions in diurnal IOP levels and a greater likelihood of achieving lower mean diurnal IOP levels. Diurnal IOP reductions of 30% or more from baseline to week 12 were achieved by 73.5%, 57.5%, and 32.8% of those treated with FCLT, latanoprost, and timolol, respectively (P = .007 for FCLT vs timolol; P < .001 for FCLT vs latanoprost). All therapies were well tolerated. CONCLUSIONS: Fixed-combination latanoprost-timolol therapy is as safe and effective in lowering IOP in patients with either ocular hypertension or glaucoma as monotherapy with latanoprost or timolol. Combination therapy can be used to treat patients for whom monotherapy does not provide sufficient IOP reduction. APPLICATION TO CLINICAL PRACTICE: The simplicity, efficacy, and tolerability of FCLT contribute to its utility in clinical practice. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00277498.

Relationship between visual field severity and response to fixed combination dorzolamide/timolol or timolol alone.

PURPOSE: To examine the response to intraocular pressure (IOP)-lowering medications as a function of glaucoma severity represented by visual field defects. METHODS: Post hoc analysis of a multicenter, double-masked, parallel study comparing the 24-h efficacy of the dorzolamide/timolol fixed combination (N = 117) versus timolol alone (N = 115) in patients with open-angle glaucoma or ocular hypertension. Visual field scoring was performed independently by three glaucoma specialists. Two scoring systems were used: the Advanced Glaucoma Intervention Study (AGIS) scoring system and a classical visual field scoring system. Patients were divided into three groups based on their visual field scores. The changes from baseline daytime and nighttime mean IOP, and 24-h IOP fluctuation after 8 weeks of treatment by baseline glaucoma severity, were compared across treatments using a simple linear regression analysis. RESULTS: Most (approximately 73%) patients had no visual field damage at baseline. With either dorzolamide/timolol or timolol alone, there was no significant difference in IOP response from baseline over 24 h based on the level of visual field damage, as measured by either the AGIS or the classic visual field scoring systems. The Pearson's rho correlations between the baseline AGIS score and the change in daytime IOP, nighttime IOP, and 24-h IOP range were 0.0024 (P = 0.97), -0.086 (P = 0.21), and 0.076 (P = 0.26), respectively. Correlations by classic score were 0.024 (P = 0.72), -0.074 (P = 0.28), and 0.061 (P = 0.37), respectively. CONCLUSIONS: This analysis showed no significant relation between the severity of baseline visual field defects and the ocular hypotensive efficacy of the dorzolamide/timolol fixed combination and timolol alone.