Noninferiority Study Comparing Latanoprost 0.005% Without Versus With Benzalkonium Chloride in Open-Angle Glaucoma or Ocular Hypertension

Abstract

Objectives: To evaluate the noninferiority of intraocular pressure (IOP)lowering latanoprost without benzalkonium chloride (BAK) versus latanoprost with BAK (for treatment of open-angle glaucoma or ocular hypertension). Methods: Overall, 578 patients were randomized 1:1 to latanoprost without BAK or latanoprost with BAK once daily in the affected eye(s) for 12 weeks. The primary efficacy endpoint was IOP, measured on days 0, 7, 28, 56, and 84 (8 AM, 10 AM, and 4 PM). Noninferiority was established if the following criteria were met: 95% confidence interval (CI) of the mean difference between treatments included 0 mm Hg for all time points (N1), 95% CI upper limit less than 1.5 mm Hg (N2), and less than 1 mm Hg for$7 of 12 time points (N3). Primary efficacy analysis was performed on the intent-to-treat population. Safety measurements included ocular and systemic adverse event (AE).Results: The 95% CI included 0 mm Hg for 7/12 time points (N1), 95% CI upper limit was less than 1.5 mm Hg for 12/12 time points (N2), and less than 1.0 mm Hg for 4/7 time points (N3). AEs were mild and similarly distributed between groups. Conclusions: Latanoprost without BAK did not meet two of three criteria for noninferiority and showed a similar safety profile relative to latanoprost with BAK.

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

“…The current findings are consistent with other recent publications that collectively support the safety, tolerability, and high rates of patient satisfaction and self-reported quality of life with BAK-free latanoprost formulations, including preservativefree formulations. [8][9][10][11][12][13][14][15] Results of the 12-week primary phase 3 study comparing latanoprost 0.005% without vs with BAK in OAG or OHT, which enrolled 578 patients, demonstrated that substantial reductions from baseline in IOP were maintained for the duration of the study in the latanoprost BAK-free group. 8 TEAEs were mostly mild with comparable incidence between treatment groups, and no significant safety concerns were found for ocular TEAEs (eye pain, ocular and conjunctival hyperemia, VA, eye lid and margin, cornea, anterior chamber, eye pruritus, VF, and iris and eyelash changes) in patients receiving BAK-free latanoprost.…”

“…[8][9][10][11][12][13][14][15] Results of the 12-week primary phase 3 study comparing latanoprost 0.005% without vs with BAK in OAG or OHT, which enrolled 578 patients, demonstrated that substantial reductions from baseline in IOP were maintained for the duration of the study in the latanoprost BAK-free group. 8 TEAEs were mostly mild with comparable incidence between treatment groups, and no significant safety concerns were found for ocular TEAEs (eye pain, ocular and conjunctival hyperemia, VA, eye lid and margin, cornea, anterior chamber, eye pruritus, VF, and iris and eyelash changes) in patients receiving BAK-free latanoprost. 8 A post hoc pooled analysis of 3 randomized controlled clinical trials and 2 international real-world evidence observational studies including 3610 total patients, which compared patient tolerance and efficacy of preservative-free and preservative-containing latanoprost formulations, found that patients receiving preservative-free latanoprost had reductions in conjunctival hyperemia and ocular surface disease composite score as compared with patients receiving latanoprost with preservatives.…”

“…6 , 7 In a phase 3 noninferiority study lasting 12 weeks, latanoprost BAK-free showed IOP reduction similar to that of latanoprost with BAK in patients with OAG or OHT. 8 The distribution of AEs was similar between the groups and primarily consisted of ocular events, most commonly eye pain and ocular hyperemia. 8 While these results are promising, it is also important to demonstrate that the safety of latanoprost 0.005% BAK-free is maintained beyond the 12 weeks evaluated in the noninferiority study, due to the chronic and progressive nature of glaucoma and the necessity of long-term treatment.…”

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

“…The authors concluded that the bioequivalence of the formulations was not achieved. They reported a greater reduction in IOP in the group of patients using BAK-containing formulations [8].…”

“…If preservative-free formulations (the study group) are not as efficient as preservative-containing formulations, then, since the active ingredient is the same, drug efficacy depends on the presence of the preservative. Wirta et al, in a study published in 2022, did not confirm the bioequivalence of a BAK-free latanoprost with latanoprost containing BAK at 0.05% concentration [8]. In the study, patients were randomly assigned in a ratio of 1 : 1 to either a group without BAK or to a reference group with BAK.…”