A once-daily dose of omidenepag isopropyl showed the same significance as twice-daily dosing and was more tolerable for patients.
Study design
This was a phase 2, randomized, double-masked, multicenter, parallel-arm study in which subjects were randomized 1:1 to receive omidenepag isopropyl 0.002% once daily (n = 50) or twice daily (n = 48) for 6 weeks after a washout period. The primary efficacy endpoint was the IOP in the study eye at 8:00 AM, 12:00 PM, and 4:00 PM at weeks 2 and 6. Safety endpoints included incidence of ocular and systemic adverse events, best corrected visual acuity, slit-lamp biomicroscopy findings, and ophthalmoscopy.
Outcomes
The BID dosing arm achieved lower IOP at every measured time point, though the amount was not statistically significant, likely owing in part to small sample size. Percentage of IOP reduction across all time points ranged from −28.66 ± 1.80% to −29.17 ± 1.87% in the BID arm, and from −25.55 ± 1.75% to −27.35 ± 1.77% in the QD arm. Adverse effects were more frequent in the BID arm (41.7%) than in the QD arm (14.0%). Conjunctival hyperemia was the most commonly reported adverse event, occurring in 12% of the BID group and none of the QD group. Four subjects, all from the BID group, dropped out of the study due to adverse effects.
Limitations
As a phase 2 trial, there was no placebo or active-comparator arm, and the number of study participants was limited. Rare and long-term adverse reactions were unlikely to be revealed in this trial. Exam findings of the ocular surface and adnexae were evaluated by investigator report rather than by systematic, independently graded photos, which along with limited follow-up time may underestimate the presence of periorbitopathy or pigmentation changes.
Clinical significance
Omidenepag isopropyl 0.002% is a highly selective, non-prostaglandin prostanoid EP2 receptor agonist and a promising novel glaucoma drug. Twice-daily dosing was not significantly more efficacious compared with once-daily dosing, and once-daily dosing was much more tolerable in terms of adverse effects. If and when this drug comes to market, once-daily dosing will likely be the preferred administration schedule.