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

Abstract Background: This study aimed to evaluate the non-inferiority and safety of a newly developed preservative-free (PF) multi-dose latanoprost/timolol ophthalmic solution, compared with the benzalkonium chloride (BAK)-preserved fixed combination, in patients with open-angle glaucoma and ocular hypertension. Methods: A Phase III randomized multi-center observer-blind parallel-group clinical trial was conducted. A total of ۲۱۰ adult patients (aged over ۱۸ years) were randomly treated with the PF- or the BAK-preserved latanoprost/timolol solution once daily in the affected eye(s) for ۱۲ weeks. Follow-up visits were scheduled at weeks ۲, ۶, and ۱۲; intraocular pressure (IOP) was recorded at ۸:۰۰ AM, ۱۲:۰۰ PM, and ۴:۰۰ PM. The primary efficacy endpoint to prove non-inferiority was the IOP change at ۸:۰۰ AM (± ۱ hour) from the baseline to the end of treatment (week ۱۲) in the studied eye. Safety parameters were also assessed. Results: In total, ۱۹۶ patients completed the study. The pressure-lowering effect of the PF eye drops was comparable to that of the preserved formulation at all time points. Latanoprost/timolol PF formulation was non-inferior to the BAK-preserved solution as shown by the change in IOP from day ۰ to week ۱۲. The point estimate of the inter-treatment difference was ۰.۶۲۴ mmHg (۹۵% CI: -۰.۰۹۴, ۱.۳۴۱). Both treatments were well-tolerated during the study, and they had similar adverse event profiles. Conclusions: PF-latanoprost/timolol combination was found to be non-inferior to the BAK-preserved formulation based on the efficacy at all times, with similar local tolerance.