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

Clinical Ophthalmology (Auckland, N.Z.) · 6 authors, 6 centres

AI SUMMARY

FIDELITY 100%

POPULATIONPatients with primary open-angle glaucoma or ocular hypertension with intraocular pressure ≤18 mm Hg on latanoprost monotherapy.

INTERVENTIONPreservative-free latanoprost 0.005% (T2345) administered once daily.

COMPARISONBenzalkonium chloride-preserved latanoprost 0.005% (BPL) administered once daily.

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

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TL;DR

This Phase 3 randomized trial compared preservative-free latanoprost (T2345) to benzalkonium chloride-preserved latanoprost (BPL) in 335 patients with glaucoma or ocular hypertension, finding both maintained clinically meaningful intraocular pressure control. T2345 showed a lower incidence of ocular adverse events (13.9% vs 22.5% for BPL) but did not meet all pre-specified noninferiority criteria for efficacy due to a low baseline intraocular pressure in the study population.

Full summary

1,511 CHARS

This US Phase 3 trial evaluated the noninferiority of preservative-free latanoprost 0.005% (T2345) to benzalkonium chloride-preserved latanoprost 0.005% (BPL) in patients with primary open-angle glaucoma or ocular hypertension. A key limitation was the low baseline intraocular pressure (IOP) in the study population, with mean diurnal values of 18.8 mm Hg in the T2345 group and 19.2 mm Hg in the BPL group after washout. The primary efficacy analysis in the per-protocol population showed that while the 95% confidence interval for the IOP difference between groups was within the ±1.5 mm Hg margin at all 9 time points, it did not meet the second criterion of being within ±1.0 mm Hg for the majority of time points. However, both treatments provided clinically meaningful IOP reductions, with mean diurnal IOP at Day 84 of 16.3 mm Hg for T2345 and 15.7 mm Hg for BPL. Regarding safety, T2345 demonstrated a more favorable ocular tolerance profile, with fewer patients experiencing ocular treatment-emergent adverse events (13.9% for T2345 vs. 22.5% for BPL) and treatment-related ocular adverse events (5.5% vs. 11.8%). The most common ocular events were instillation site pain and conjunctival hyperemia. The study had notable limitations, including a relatively small sample size and a short, variable washout period that contributed to the low baseline IOP. Despite not meeting all noninferiority criteria in the primary analysis, the FDA approved T2345 based on this trial and other supporting evidence.

PICO

PPOPULATION

Patients with primary open-angle glaucoma or ocular hypertension with intraocular pressure ≤18 mm Hg on latanoprost monotherapy.

IINTERVENTION

Preservative-free latanoprost 0.005% (T2345) administered once daily.

OOUTCOME

Primary efficacy was the between-group comparison of mean intraocular pressure values. Safety included ocular and systemic treatment-emergent adverse events.

STUDY TYPE

RCT

SPECIALTY

ophthalmology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10478989

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

Clinical Ophthalmology (Auckland, N.Z.)

READ THE FULL PAPER

ABSTRACT

Abstract Purpose 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

CITATION EXPORT

Jason Bacharach, Iqbal Ike K Ahmed, Elizabeth D Sharpe et al.. 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. Clinical Ophthalmology (Auckland, N.Z.). (2023). https://doi.org/10.2147/OPTH.S414015

AUTHORS

6 · 6 CENTRES

Jason Bacharach, Iqbal Ike K Ahmed, Elizabeth D Sharpe, Michael S Korenfeld, Steven Zhang, Christophe Baudouin

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, France