Bioequivalence of Preservative-free and Preserved Omidenepag Isopropyl (OMDI) 0.002% Ophthalmic Solutions in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: Results from the Phase 3 DAISY Study.

Abstract

Prcis: Preservative-free omidenepag isopropyl (OMDI) 0.002% ophthalmic solution and OMDI 0.002% ophthalmic solution preserved with benzalkonium chloride were bioequivalent in lowering intraocular pressure after 4 weeks' treatment in patients with primary open-angle glaucoma or ocular hypertension.

Purpose: Preservatives in ophthalmic solutions for lowering intraocular pressure (IOP) are associated with ocular surface disease. The DAISY study evaluated the bioequivalence of preservative-free omidenepag isopropyl (OMDI) 0.002% ophthalmic solution (DE-117B), with OMDI 0.002% preserved with benzalkonium chloride (BAK).

Methods: DAISY was a phase 3, randomized, evaluator-masked, crossover study conducted in Japan. Patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) were randomized 1:1 to DE-117B or OMDI 0.002% for 4 weeks (period 1) then crossed over for 4 weeks (period 2). A 4-week washout preceded both periods. The primary efficacy endpoint was mean diurnal (MD) IOP at Week 4 (combined periods 1 and 2). Bioequivalence between DE-117B and OMDI was defined as 95% confidence interval (CI) between -1.5 and 1.5 for least-squares (LS) mean between-group difference in MD IOP. Adverse events were monitored.

Results: Of 74 patients enrolled, 38 were randomized to DE-117B then OMDI, and 36 were randomized to OMDI then DE-117B. DE-117B and OMDI demonstrated bioequivalence at Week 4 (MD IOP±standard deviation in summary statistics: 17.76±2.05 mm Hg [DE-117B] vs. 17.71±2.01 mm Hg [OMDI]; LS mean±standard error between-group difference in linear mixed effects model: -0.02±0.18 mm Hg [95% CI -0.38 to 0.35]). DE-117B versus OMDI was associated with numerically lower overall ocular discomfort.

Conclusions: Preservative-free DE-117B and BAK-containing OMDI were bioequivalent in lowering IOP after 4 weeks' treatment in Japanese patients with POAG or OHT. DE-117B was well tolerated with a similar safety profile to OMDI.