Open-Label Extension Study Comparing Latanoprost 0.005% Without vs With Benzalkonium Chloride in Open-Angle Glaucoma or Ocular Hypertension

Abstract

Purpose To evaluate the long-term safety of latanoprost benzalkonium chloride (BAK)-free vs currently marketed latanoprost 0.005% ophthalmic solution containing BAK (referred to as reference), to treat open-angle glaucoma (OAG) or ocular hypertension (OHT). Patients and Methods This phase 3, multicenter, open-label, nonrandomized, single group assignment, safety study included patients who previously completed a phase 3 noninferiority study. Patients self-administered 1 drop of latanoprost BAK-free nightly for 36 weeks in the affected eye(s). Intraocular pressure (IOP), visual acuity (VA), and slit lamp biomicroscopy were assessed predose at baseline and Days 28, 56, 84, 112, 140, and 168; dilated ophthalmoscopy and visual field (VF) at baseline and Day 168. Adverse events (AEs) were recorded throughout the study. Results A total of 161 patients who previously received latanoprost BAK-free (n = 80) or reference (n = 81) were enrolled. Latanoprost BAK-free maintained lowered IOP for both the study and nonstudy eye in all patients relative to baseline throughout the study. Clinically significant retinal or optic nerve changes were identified in 5 patients (1 mild-to-moderate change, prior latanoprost BAK-free; 4 mild changes, prior reference). No clinically important changes were identified for VA, slit lamp biomicroscopy, and VF measurements. Ocular AEs occurred in 66 (82.5%) vs 74 (91.4%) patients on prior latanoprost BAK-free and reference, respectively; the most frequent being eye pain (50.0% vs 64.2%) and ocular hyperemia (47.5% vs 54.3%). Most AEs were mild. There were 5 serious systemic AEs in 5 patients (n = 3, prior latanoprost BAK-free; n = 2, prior reference); all were considered unrelated or not likely related to treatment. One patient (prior reference) discontinued due to follicular conjunctivitis. There were no deaths or serious ocular AEs. Conclusion Latanoprost BAK-free was well tolerated. These findings support the chronic use of latanoprost BAK-free to treat OAG or OHT. Clinical Trial Registration Number NCT00945958.

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

“…This study also demonstrated a mean ± SD IOP reduction in the study eye of 8.6 ± 2.6 mm Hg (~36%) at Day 84 (versus baseline) in the T2345 group and 9.0 ± 2.4 mm Hg (~38%) in the BPL group in the modified ITT (mITT) population. These findings are consistent with what has been reported in phase 3 clinical trials for BPL and potassium sorbatepreserved latanoprost 0.005%, 28 with reductions of 6-8 mm Hg from baseline for both, along with IOP reductions reported for other PGAs (~25%-33%). 29,30 An important difference between these clinical trials and the current trial is the baseline IOP levels.…”

Czy konserwanty poprawiają przepuszczalność powierzchni oka, a tym samym skuteczność terapii?

“…The same formulations were studied again in July 2022 by Lee et al The authors noted a similar hypotensive effect of the two formulations; however, BAK-containing latanoprost was slightly more effective in lowering IOP. The difference was not statistically significant, but the graph presented by the authors showed a higher decrease of IOP in patients using BAK-containing preparations [9]. In 2021, Skov et al published a meta-analysis that evaluated studies comparing the hypotensive effect of β-blocker timolol with and without preservatives.…”

“…Similarly, authors of the second study reported more adverse effects in patients using BAK-free formulations (893 vs. 827). Therefore, it can be concluded that preservatives in ophthalmic drops do not affect their safety or the number of adverse effects [9]. In the meta-analysis, the level of evidence for all ocular surface outcomes was low or very low and reported in only a few studies.…”

“…Authors of the studies [8,9] examining the efficacy of IOP-lowering medications, evaluated their safety by assessing the number of adverse effects during their use. Wirta et al found that patients using preservative-free formulations reported more adverse effects, including significantly more serious adverse ones (18 vs. 8) [8].…”