Preservative-Free versus Benzalkonium Chloride–Preserved Latanoprost Ophthalmic Solution in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: A Phase 3 US Clinical Trial

Jason Bacharach,1 Iqbal Ike K Ahmed,2 Elizabeth D Sharpe,3 Michael S Korenfeld,4 Steven Zhang,5 Christophe Baudouin6 1North Bay Eye Associates, Sonoma County, CA, USA; 2John Moran Eye Center, University of Utah, Salt Lake City, UT, USA; 3Glaucoma Consultants and Center for Eye Research, Mt. Pleasant, SC, USA; 4Comprehensive Eye Care, Washington, MO, USA; 5Thea Pharma, Inc, Lexington, MA, USA; 6Quinze-Vingts National Ophthalmology Hospital & Vision Institute, Paris Saclay-Versailles-Saint Quentin University, IHU Foresight, Paris, FranceCorrespondence: Jason Bacharach, Email jbacharach@northbayeye.comPurpose: To evaluate the safety and efficacy of a preservative-free latanoprost 0.005% formulation (T2345) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) compared to benzalkonium chloride–preserved latanoprost 0.005% (BPL) formulation in the United States (US).Patients and Methods: A prospective, randomized, multicenter, observer-masked, parallel-group study enrolled 335 patients diagnosed with POAG or OHT from 31 US sites who had adequately controlled intraocular pressure (IOP; ≤ 18 mm Hg) with latanoprost monotherapy. After a ≥ 72-hour washout period, patients were randomized to T2345 (n=165) or BPL (n=170) groups. Study drugs were dosed once-daily from Day 0 to Day 84 in one or both eyes. The study eye was the eye with lower IOP at baseline. The primary efficacy measure was the between-group comparison of the mean IOP values in the study eye at each time point (8 AM, 10 AM, and 4 PM on Days 15, 42, and 84). Safety measurements included ocular and systemic treatment-emergent adverse events (TEAEs).Results: Both T2345 and BPL adequately controlled IOP with 95% CIs within 1.5 mm Hg in the study eye at all assessed time points. The percentages of patients with diurnal IOP < 18 mm Hg at Day 84 were 73.1% vs 78.7% for the T2345 and BPL groups, respectively. Adverse events were generally mild-to-moderate and primarily ocular. Fewer patients in the T2345 group experienced ocular TEAEs (13.9% vs 22.5%, respectively) and TEAEs with a suspected relationship to the study medication compared with the BPL group (5.5% vs 11.8%, respectively). The most common ocular TEAEs were instillation site pain and conjunctival hyperemia.Conclusion: In patients with POAG or OHT, both T2345 and BPL maintained IOP at or below clinically meaningful values for the duration of the study. T2345 showed a favorable safety profile, with numerically lower incidences of ocular TEAEs than BPL.Keywords: glaucoma, ocular hypertension, intraocular pressure, benzalkonium chloride, latanoprost, preservative