Browsing by Subject "ONO-9054"

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    Ocular Hypotensive Effect of ONO-9054, an EP3/FP Receptor Agonist: Results of a Randomized, Placebo-controlled, Dose Escalation Study
    (Lippincott, Williams, and Wilkins, 2016-10) Harris, Alon; Ward, Caroline L.; Rowe-Rendleman, Cheryl L.; Ouchi, Takafumi; Wood, Andrew; Fujii, Akifumi; Serle, Janet B.; Department of Ophthalmology, IU School of Medicine
    Purpose: To assess pharmacodynamic and safety profiles of ONO-9054 following single and multiple day dosing in subjects with ocular hypertension or open-angle glaucoma. Materials and Methods: This was a phase I, single-center, randomized, double-masked, placebo-controlled dose-escalation study. Nine subjects were randomized to each of ONO-9054 3, 10, 20, 30 μg/mL and 12 to placebo. Subjects received a single drop to each eye at 07:00±30 minutes (single dose). Following a 4-day no-treatment period, subjects were dosed once daily for 14 consecutive days (multiple day dosing). Intraocular pressure (IOP) was measured regularly and compared with baseline measurements. Ocular examinations assessed safety and tolerability. Results: Mean IOP decreased dose dependently. Following single dosing, IOP decreased from 22.9±4.0 to 15.9±2.3 mm Hg (ONO-9054, 30 μg/mL) at peak effect 9 hours postdose; the reduction in placebo-treated subjects was from 22.3±2.4 to 21.5±3.3 mm Hg. Following multiple day dosing, the greatest reduction in IOP occurred 1 hour postdose on day 18, from 23.3±0.6 to 15.1±2.4 mm Hg (ONO-9054, 10 μg/mL); the smallest reduction at this time was from 23.9±0.8 to 18.6±2.0 mm Hg (ONO-9054, 3 μg/mL). Pressures remained reduced on day 19, 25 hours after the last dose, when the lowest measurement was 15.8±2.1 mm Hg (ONO-9054, 10 μg/mL). Anterior uveitis and vitreous detachment were each reported in 2 subjects and considered moderate by the Investigator. Ocular hyperemia and tolerability symptoms were generally mild and transient. Conclusions: ONO-9054 was well-tolerated and elicited dose-dependent reductions in IOP, which were sustained for at least 24 hours following 2 weeks of consecutive daily dosing.
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    Ocular hypotensive effect of the novel EP3/FP agonist ONO-9054 versus Xalatan: results of a 28-day, double-masked, randomised study
    (BMJ, 2016) Ellis, Eydie Miller; Berlin, Michael S.; Ward, Caroline L.; Sharpe, John A.; Jamil, Alam; Harris, Alon; Department of Ophthalmology, IU School of Medicine
    Background/aims ONO-9054 is being developed for the reduction of intraocular pressure (IOP) in patients with ocular hypertension (OHT) and open-angle glaucoma (OAG). This study compared the novel dual EP3/FP agonist ONO-9054 with the FP agonist Xalatan. Methods Adults (n=123) with bilateral mild/moderate OAG or OHT, with unmedicated IOP of ≥24 mm Hg at 8:00 hours, ≥21 mm Hg at 10:00 hours and ≤36 mm Hg, were randomised 1:1 to receive ONO-9054 (0.003%, 30 μg/mL) or Xalatan (0.005%, 50 μg/mL) once daily for 28 days. Results Day 29 mean diurnal IOP was −7.2 mm Hg for ONO-9054 vs −6.6 mm Hg for Xalatan. At 08:00 hours, the IOPs were comparable, and at all later time points the decrease in IOP was greater for ONO-9054. On day 29, the odds of a mean IOP reduction of ≤−25%, ≤−30% and ≤−35% for ONO-9054 were 2.39, 2.37 and 4.85 times more, respectively, than the odds for Xalatan (p<0.05, post hoc analyses). The percentage of subjects achieving target IOPs on day 29 (≤17, ≤16 and ≤15 mm Hg) was greater for ONO-9054 than for Xalatan; the odds of achieving an IOP ≤15 mm Hg for ONO-9054 were 2.4 times more than the odds for Xalatan (p<0.01, post hoc analysis). Conclusions Subjects randomised to receive ONO-9054 were more likely to achieve a greater per cent reduction in IOP and were more likely to achieve target IOPs than those receiving Xalatan. The effects of ONO-9054 in reducing IOP appear to persist longer than those of Xalatan.