title: 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: OBJECTIVE
  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.
  
  
  BACKGROUND
  NCT01670266.
authors.affiliation: Glaucoma Institute of Beverly Hills & UCLA, Los Angeles, California, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Berlin
authors.affiliation: Ono Pharma-USA, Lawrenceville, New Jersey, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Rowe-Rendleman
authors.affiliation: Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ike
authors.initials: I
authors.lastname: Ahmed
authors.affiliation: Ono Pharma-USA, Lawrenceville, New Jersey, USA.
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Ross
authors.affiliation: Ono Pharma-USA, Lawrenceville, New Jersey, USA.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Fujii
authors.affiliation: Ono Pharma-USA, Lawrenceville, New Jersey, USA.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ouchi
authors.affiliation: Glaucoma Institute of Beverly Hills & UCLA, Los Angeles, California, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Quach
authors.affiliation: Ono Pharma-USA, Lawrenceville, New Jersey, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wood
authors.affiliation: Ono Pharma UK Ltd, London, UK.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Ward
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009883:Ophthalmic Solutions; D010082:Oxepins / Q000008:administration & dosage*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009883:Ophthalmic Solutions; D010082:Oxepins; D011982:Receptors, Prostaglandin; D058308:Receptors, Prostaglandin E, EP3 Subtype; C034671:prostaglandin F2alpha receptor; C000607345:propan-2-yl 4-(6-(4-(2,5-difluorophenoxy)-3-hydroxybut-1-en-1-yl)-7-hydroxyoctahydro-2H-cyclopenta(b)oxepin-3-yl)butanoate
keywords: Glaucoma; Intraocular pressure; Pharmacology