Randomized Clinical Trial Of The Efficacy And Safety Of Preservative-free Tafluprost And Preservative-free Timolol In Patients With Open-angle Glaucoma (OAG) Or Ocular Hypertension (OHT)

Abstract

Purpose: : Prostaglandin analogs are first-line IOP-lowering therapy in patients with OAG and OHT. Most topical ocular hypotensives contain the preservative benzalkonium chloride, which may be associated with decreased ocular tolerability in some patients. We compared the efficacy and safety of tafluprost, a preservative-free (PF) prostaglandin analog, with PF timolol.

Methods: : Randomized, double-masked, Phase III clinical trial (NCT01026831) in patients with OAG and OHT. After discontinuation and washout of existing ocular hypotensive treatment, patients who had IOP ≥23 and ≤36 mmHg in at least 1 eye at the 0800 hr time point were randomized 1:1 to 12 weeks of treatment with either PF tafluprost (PF TAF) 0.0015% or PF timolol (PF TIM) 0.5%. IOP was measured 3 times during the day (0800, 1000, 1600 hrs) at baseline and week 2, 6, and 12. The primary hypothesis was that PF TAF would be non-inferior to PF TIM in IOP change from baseline at all visits and time points (9 time points). The study was powered for a non-inferiority margin of 1.5 mmHg.

Results: : A total of 643 patients were randomized and 618 completed (PF TAF = 306, PF TIM = 312). Baseline IOPs ranged from 23.8-26.1 mmHg in the PF TAF group and 23.5-26.0 mmHg in the PF TIM group. IOPs at the 12-week visit ranged from 17.4-18.6 mmHg for PF TAF and 17.9-18.5 mmHg for PF TIM. At all 9 time points, the upper limits of the 2-sided 95% CIs for the difference between treatments in IOP-lowering were less than the pre-specified non-inferiority margin; at 4 of the 9 time points, the upper limits of the CIs were < 0, in favor of PF TAF. Similar percentages of PF TAF and PF TIM patients reported ocular pain/stinging/irritation (4.4% vs. 4.6%) and pruritus (2.5% vs. 1.5%). The percentages of PF TAF and PF TIM patients reporting conjunctival hyperemia were 4.4% vs. 1.2% (nominal p=0.016).

Conclusions: : The IOP-lowering effect of PF tafluprost was non-inferior to that of PF timolol. PF tafluprost is an efficacious and generally well-tolerated ocular hypotensive agent.

Clinical Trial: : http://www.clinicaltrials.gov NCT01026831

Keywords: intraocular pressure • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • ocular irritants