Bioequivalence of Preservative-Free and Preserved Omidenepag Isopropyl 0.002% Ophthalmic Solutions in Patients With Primary Open Angle Glaucoma or Ocular Hypertension: Phase 3 DAISY Study

PRÉCIS: Preservative-free omidenepag isopropyl (OMDI) 0.002% ophthalmic solution and OMDI 0.002% ophthalmic solution preserved with benzalkonium chloride (BAK) were bioequivalent in lowering intraocular pressure (IOP) after 4 weeks' treatment in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). OBJECTIVE: Preservatives in ophthalmic solutions for lowering IOP are associated with ocular surface disease. The DAISY study evaluated the bioequivalence of preservative-free OMDI 0.002% ophthalmic solution (DE-117B), with OMDI 0.002% preserved with BAK. METHODS: DAISY was a phase 3, randomized, evaluator-masked, crossover study conducted in Japan. Patients with POAG or OHT were randomized 1:1 to DE-117B or OMDI 0.002% for 4 weeks (period 1) and 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 a 95% CI between -1.5 and 1.5 for least squares 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 ± SD in summary statistics: 17.76 ± 2.05 mm Hg (DE-117B) vs 17.71 ± 2.01 mm Hg (OMDI); least squares mean ± SE between-group difference in linear mixed effect 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.