Pharmacokinetics, Safety and IOP Lowering Profiles of omidenepag isopropyl, a Selective EP2 Agonist in Healthy Japanese and Caucasian Volunteers (Phase I Study)

Abstract

Purpose : To evaluate the plasma pharmacokinetics, safety and intraocular pressure (IOP) lowering profiles of omidenepag isopropyl (OMDI) ophthalmic solution 0.0025%, one drop once daily for 7 days, in healthy male adults.

Methods : This was a Phase I open-label, single center study. Fourteen (14) healthy male volunteers were enrolled including 7 Japanese and 7 Caucasian. OMDI 0.0025% was administrated once daily at 9:00 a.m. for 7 days. The plasma concentrations and pharmacokinetic parameters (C_max, T_max, T_1/2, and AUC_inf) of omidenepag (OMD), the active metabolite of OMDI were determined. Adverse events, ocular and systemic safety parameters were analyzed. IOP was measured.

Results : The shapes of the plasma concentration of OMD over time were similar for study Days 1, 3 and 7 in both Japanese and Caucasian subjects. There were no significant differences in pharmacokinetic parameters between Japanese and Caucasian subjects after repeated dosing (7 days). The pharmacokinetic results (mean ± SD) on day 7 for Japanese and Caucasian subjects were, respectively: C_max 37.53 ± 15.52 pg/mL vs 33.31 ± 11.81 pg/mL; AUC_inf 24.49 ± 6.43 pg*h/mL vs 20.02 ± 4.81 pg*h/mL; T_max 0.20 ± 0.08 hours vs 0.18 ± 0.09 hours; T_1/2 0.49 ± 0.07 hours vs. 0.53 ± 0.09 hours. The OMD concentrations were below the limit of quantification (BLQ, < 1.00 pg/mL) after 4 hours of administration for all Japanese and Caucasian subjects on Days 1, 3 and 7. There were no unexpected safety findings. There were 3 (21.4%) subjects with conjunctival hyperemia, 2 (14.3%) subjects with photophobia and 1 (7.1%) subject with AST/ALT increase. These adverse events (AEs) were mild but study drug related and resolved within 4 days for ocular AEs and within 8 days for systemic AEs without intervention. IOP reduction was observed as early as 2 hours after dosing, reached the maximal effect and stable from day 3 onwards. After 7 days of dosing, mean diurnal IOP reduction, on average, was 4.92 ± 1.37 mmHg vs. 5.41 ± 1.67 mmHg in Japanese and Caucasian subjects, respectively.

Conclusions : The pharmacokinetic parameters were similar between Japanese and Caucasian subjects. There was no OMD accumulation in plasma after 7 days of repeated dosing. OMDI was well tolerated. OMDI 0.0025% demonstrated good IOP-lowering effect in both Japanese and Caucasian healthy volunteers.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.