Abstract
Purpose :
It was hypothesized that ONO-9054, a potent dual EP3/FP prostanoid receptor agonist, might provide a greater and more sustained reduction in IOP than the FP agonist latanoprost. This Phase II study compared the effects of once daily evening (22:00) dosing of ONO-9054 (0.003%, 30 μg/mL) to latanoprost (Xalatan®; 0.005%, 50 μg/mL) in mild to moderate OAG or OHT.
Methods :
Adults with un-medicated IOP ≥ 24 mmHg at 8:00 AM and ≥ 21mmHg at 10:00 AM were randomized 1:1 to ONO-9054 or Xalatan®. Exclusion criteria included: history of severe ocular trauma; narrow angles grade ≤ 2. Study powered (≥ 80%) to detect a difference between treatments at the significance level of 0.05.
Results :
62 Subjects randomized to ONO-9054 and 61 to Xalatan®. There were 37 adverse events (AEs) in 22 ONO-9054 subjects and 35 AEs in 18 Xalatan® subjects; all mild or moderate in intensity. One unrelated SAE (NAION) occurred in a subject randomized to receive ONO-9054. Tolerability scores were similar between the groups. Individual subject hyperemia scores were similar between ONO-9054 and Xalatan® groups, however, the number of hyperemia AEs reported for ONO-9054 was higher than reported for Xalatan® (19.4% vs 8.2%). Hyperemia AEs in both groups resolved without sequelae and hyperemia symptoms had returned to baseline levels by follow-up.
ONO-9054 achieved a greater reduction in mean diurnal IOP at Day 29 (08:00, 10:00, 12:00 and 16:00; mean reduction -7.2 mmHg vs. -6.6 mmHg) but this was not statistically significant. Statistical significance was achieved at Day 29 at 10:00, 12:00, 16:00 and 20:00 combined (P<0.05, post hoc analysis). Both treatments were similarly effective at the 08:00 hour assessment but there was a greater and more prolonged effect for ONO 9054 compared to Xalatan® throughout the day. At 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 for Xalatan® [P<0.05, post hoc analysis]. The odds of achieving a target IOP ≤15 mmHg for ONO-9054 were 2.4 times more than for Xalatan® [P<0.01, post hoc analysis].
Conclusions :
Subjects randomized to receive ONO-9054 were more likely to achieve a significantly larger reduction in IOP with longer duration of efficacy than those receiving Xalatan®.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.