Non-inferiority evaluation of preservative-free latanoprost/timolol eye drops solution versus preserved latanoprost/timolol eye drops in patients with high intraocular pressure and open-angle glaucoma

This study aimed to evaluate the non-inferiority and safety of a newly developed preservative-free (PF) multi-dose latanoprost/timolol ophthalmic solution, compared withthe benzalkonium chloride (BAK)-preserved fixed combination,in patients with open-angle glaucoma and ocular hypertension.

A Phase III randomized multi-center observer-blind parallel-group clinical trial was conducted. A total of 210 adult patients (aged over 18 years) were randomly treated withthe PF-or the BAK-preserved latanoprost/timolol solution once daily in the affected eye(s) for 12 weeks. Follow-up visits were scheduled at weeks 2, 6,and 12;intraocular pressure (IOP) was recorded at 8:00AM, 12:00 PM,and 4:00 PM. The primary efficacy endpoint to prove non-inferiority was the IOP changeat 8:00 AM(± 1 hour) from the baseline to the end of treatment (week 12) in the studiedeye. Safety parameters were also assessed.

In total,196 patients completed the study. The pressure-lowering effect of thePF eye drops was comparable to that of the preservedformulation at all-timepoints. Latanoprost/timolol PFformulation was non-inferior to the BAK-preserved solution as shown by the change in IOP from day 0 to week 12. The point estimate of the inter-treatment difference was 0.624 mmHg(95% CI: -0.094, 1.341). Both treatments were well-tolerated during the study, and they hadsimilar adverse event profiles.

PF-latanoprost/timolol combination was found to be non-inferior to the BAK-preserved formulationbased onthe efficacyat all times,with similar local tolerance.