Phase 2, Randomized, Dose-finding Studies of Omidenepag Isopropyl, a Selective EP2 Agonist, in Patients With Primary Open-angle Glaucoma or Ocular Hypertension.
Aihara Makoto, Lu Fenghe, Kawata Hisashi, Iwata Akihiro, Liu Kathy, Odani-Kawabata Noriko, Shams Naveed K
AI Summary
Omidenepag isopropyl effectively lowered IOP in glaucoma/ocular hypertension patients, with 0.002% identified as the optimal, well-tolerated dose for further study, offering a new potential treatment option.
Abstract
Unlabelled: PRéCIS:: Three randomized, multicenter studies demonstrated the stable intraocular pressure-lowering effects and tolerability of omidenepag isopropyl in patients with primary open-angle glaucoma and ocular hypertension; 0.002% was identified as the optimal dose for further investigation.
Purpose
The purpose of this study was to assess the safety and efficacy of omidenepag isopropyl, a selective EP2 agonist, and to determine the optimal dose for further investigation.
Patients and methods: Three randomized, controlled, masked, multicenter studies were conducted in United States (study 1, NCT01868126; study 2, NCT02179008) and Japan (study 3, NCT02623738). Patients were randomized to 1 of 7 omidenepag isopropyl concentrations (0.0003%, 0.001%, 0.0012%, 0.0016%, 0.002%, 0.0025%, and 0.003%), latanoprost (0.005%), or placebo, 1 drop once daily for 28 days (studies 1 and 3) or 90 days (study 2). Primary endpoints were the observed mean diurnal intraocular pressure (IOP) and IOP at each time point on the final visit (studies 1 and 2) and change from baseline in mean diurnal IOP at week 4 (study 3).
Results
IOP-lowering effects of omidenepag isopropyl 0.0003% to 0.002% increased dose-dependently. Omidenepag isopropyl 0.002% and 0.0025% resulted in clinically relevant mean diurnal IOP reductions from baseline that were similar to those of latanoprost and superior to placebo (P<0.005). Maximum reductions had already been achieved by week 1, and stable IOP-lowering effects were observed at all postbaseline time points up to 3 months. Most adverse events (AEs) were mild. Conjunctival hyperemia was the most frequently reported AE, the incidence of which increased dose-dependently. The safety profiles of omidenepag isopropyl 0.002% and 0.0025% were similar, with a slightly lower incidence of AEs in the 0.002% group.
Conclusions
Omidenepag isopropyl demonstrated stable IOP-lowering effects and was well tolerated; 0.002% was identified as the optimal dose for phase 3 investigation.
MeSH Terms
Shields Classification
Key Concepts5
Omidenepag isopropyl 0.002% and 0.0025% demonstrated clinically relevant mean diurnal intraocular pressure (IOP) reductions from baseline that were similar to those of latanoprost (0.005%) and superior to placebo (P<0.005) in patients with primary open-angle glaucoma or ocular hypertension.
The IOP-lowering effects of omidenepag isopropyl at concentrations ranging from 0.0003% to 0.002% increased dose-dependently in patients with primary open-angle glaucoma or ocular hypertension.
Maximum reductions in intraocular pressure with omidenepag isopropyl were achieved by week 1, and stable IOP-lowering effects were observed at all postbaseline time points up to 3 months in patients with primary open-angle glaucoma or ocular hypertension.
Most adverse events (AEs) associated with omidenepag isopropyl were mild, with conjunctival hyperemia being the most frequently reported AE, and its incidence increased dose-dependently in patients with primary open-angle glaucoma or ocular hypertension.
The safety profiles of omidenepag isopropyl 0.002% and 0.0025% were similar, with a slightly lower incidence of adverse events in the 0.002% group, leading to the identification of 0.002% as the optimal dose for further investigation in patients with primary open-angle glaucoma or ocular hypertension.
Related Articles5
Safety and Efficacy of Omidenepag Isopropyl for Elevated Intraocular Pressure: A Systematic Review and Meta-Analysis.
Systematic ReviewA phase III study comparing preservative-free latanoprost eye drop emulsion with preserved latanoprost in open-angle glaucoma or ocular hypertension.
Randomized Controlled TrialPhase 3 Randomized Clinical Trial of the Safety and Efficacy of Travoprost Intraocular Implant in Patients with Open-Angle Glaucoma or Ocular Hypertension.
Randomized Controlled TrialThe Effect of Latanoprostene Bunod 0.024% on Optical Coherence Tomography Angiography in Newly Diagnosed Open Angle Glaucoma.
Clinical TrialAqueous Humor Dynamics Changes and Predictors of IOP Response to Latanoprost in Healthy Subjects.
Clinical TrialIs this article assigned to the wrong chapter(s)? Let us know.