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.

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.

• Authors: Michael S Berlin, Cheryl Rowe-Rendleman, Ike Ahmed, Douglas T Ross, Akifumi Fujii, Takafumi Ouchi, Christine Quach, Andrew Wood, Caroline L Ward
• Journal: The British journal of ophthalmology (Br J Ophthalmol) Vol. 100 Issue 6 Pg. 843-7 (Jun 2016) ISSN: 1468-2079 [Electronic] England
• PMID: 26453641 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: 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/

Chemical References

• Ophthalmic Solutions
• Oxepins
• Receptors, Prostaglandin
• Receptors, Prostaglandin E, EP3 Subtype
• prostaglandin F2alpha receptor
• propan-2-yl 4-(6-(4-(2,5-difluorophenoxy)-3-hydroxybut-1-en-1-yl)-7-hydroxyoctahydro-2H-cyclopenta(b)oxepin-3-yl)butanoate

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Glaucoma, Open-Angle (drug therapy, metabolism, physiopathology)
• Humans
• Intraocular Pressure (drug effects)
• Male
• Middle Aged
• Ocular Hypertension (drug therapy, metabolism, physiopathology)
• Ophthalmic Solutions
• Oxepins (administration & dosage)
• Receptors, Prostaglandin (antagonists & inhibitors)
• Receptors, Prostaglandin E, EP3 Subtype (antagonists & inhibitors)
• Treatment Outcome
• Young Adult