EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study

Michael S Berlin, Cheryl Rowe-Rendleman, Ike Ahmed, Douglas T Ross, Akifumi Fujii, Takafumi Ouchi, Christine Quach, Andrew Wood, Caroline L Ward, Michael S Berlin, Cheryl Rowe-Rendleman, Ike Ahmed, Douglas T Ross, Akifumi Fujii, Takafumi Ouchi, Christine Quach, Andrew Wood, Caroline L Ward

Abstract

Background/aims: The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering.

Methods: This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension. Two 14-day crossover regimens were separated by a 2-week washout: ONO-9054 (1 drop to each eye) in the morning (07:00) and vehicle in the evening (19:00) and vice versa. IOP was measured multiple times during select days. Ocular examinations also evaluated safety and tolerability.

Results: Mild ocular hyperaemia, reported by six subjects with PM dosing, was the most frequent adverse event. Mild to moderate dryness was also slightly more frequent after PM dosing. Maximum IOP reduction from baseline occurred on day 2 with decreases from baseline of -7.4 mm Hg (-30.8%) for AM dosing and -9.1 mm Hg, (-38.0%) for PM dosing; after 14 days, mean reduction in IOP was -6.8 mm Hg (-28.6%) for AM dosing and -7.5 mm Hg (-31.0%) for PM dosing.

Conclusions: PM dosing of ONO-0954 was associated with a slightly increased frequency of mild hyperaemia and mild to moderate dryness. Both dosing schedules provided sustained reduction in IOP.

Trial registration number: NCT01670266.

Keywords: Glaucoma; Intraocular pressure; Pharmacology.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Figures

Figure 1
Figure 1
Observed intraocular pressure (IOP) values following morning (AM) and evening (PM) dosing of ONO-9054. IOP decreased from baseline in both cohorts, and this was maintained throughout the dosing period. Data from both dosing sequences were pooled to produce data for AM (♦) and PM (▴) dosing.

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