Changes in ocular signs and symptoms in patients switching from bimatoprost-timolol to tafluprost-timolol eye drops: an open-label phase IV study

Abstract

Objectives: Bimatoprost-timolol (bimatoprost 0.03%-timolol 0.5% fixed-dose combination [FDC]) and tafluprost-timolol (tafluprost 0.0015%-timolol 0.5% FDC) eye drops are currently the only topical intraocular pressure (IOP)-reducing therapies available as preservative-free (PF) prostaglandin and timolol FDC. The aim of this study was to investigate changes to ocular signs and symptoms when patients with ocular hypertension (OH) or open-angle glaucoma (OAG) switched from PF or benzalkonium chloride (BAK)-preserved bimatoprost-timolol to PF tafluprost-timolol eye drops.

Design: This was a 12-week, open-label, phase IV study.

Setting: Sixteen centres in Finland, Germany, Italy and the UK.

Participants: Patients with OH or OAG (IOP on medication ≤21 mm Hg), treated with PF or BAK-preserved bimatoprost-timolol for ≥4 weeks before screening, and presenting with conjunctival hyperaemia and ≥1 ocular symptom.

Interventions: Patients were switched to PF tafluprost-timolol once daily in the treated eye(s).

Primary and secondary outcome measures: The primary endpoints were change from screening to week 12 in conjunctival hyperaemia and worst ocular symptom. The secondary outcome measures were changes from screening in ocular signs (other than conjunctival hyperaemia) and symptoms at week 12.

Results: Of 123 enrolled patients, 121 were included in the intention-to-treat dataset, of which all were Caucasian and 54.5% were female; 76 patients used BAK-preserved bimatoprost-timolol and 45 used PF drops. Conjunctival hyperaemia and severity of worst ocular symptom following switch to PF tafluprost-timolol significantly reduced from screening to week 12 in all patients (p<0.001). The percentage of patients with ocular signs and symptoms was significantly reduced at week 12 compared with screening (p<0.001). IOP was not affected by the change of treatment.

Conclusions: Switching from BAK-preserved or PF bimatoprost-timolol to tafluprost-timolol reduced both signs and symptoms of ocular surface disease with no clinically relevant effect on IOP.

Trial registration number: EudraCT2014-005273-37; Results.

Keywords: clinical pharmacology; clinical trials; glaucoma; intraocular pressure; medical ophthalmology; ocular surface.

Conflict of interest statement

Competing interests: RRAB has received travel expenses from Santen. KK has received a consultant fee from Santen for an advisory board. KL has no conflicts of interest to report. CET has received department funding for the conduction of this study, personal fees and non-financial support from Santen not related to this study or manuscript, and department funding from Novartis and Allergan. JV has received fees for statistical services from Santen. AR is an employee at Santen Oy.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Patient disposition by previous bimatoprost–timolol treatment. After initial screening, three patients did not meet the inclusion criteria. A total of nine (7.4%) patients discontinued the study; five discontinued because of AEs and four withdrew from the study. AE, adverse event; BAK, benzalkonium chloride; PF, preservative-free.

Figure 2

Comparison of week 12 outcomes with screening in conjunctival hyperaemia and worst ocular symptom after switching from bimatoprost–timolol to tafluprost–timolol (A) change in conjunctival hyperaemia from screening (n=121) to week 12 (n=114); (B) breakdown of changes in conjunctival hyperaemia severity by subgroup at week 12 compared with screening. One patient in the ITT dataset violated inclusion criterion 2 and only had mild conjunctival hyperaemia at screening; (C) severity of worst ocular symptom at screening and week 12 in all patients; and (D) changes in severity of worst ocular symptom by subgroup at week 12 compared with screening. BAK, benzalkonium chloride; ITT, intention-to-treat; PF, preservative-free.

Figure 3

Secondary endpoints (A) abnormal ocular signs at screening (n=121); (B) abnormal ocular signs at week 12 (n=114); (C) abnormal ocular symptoms at screening; (D) abnormal ocular symptoms at week 12. BAK, benzalkonium chloride; PF, preservative-free.