Pharmacokinetics, Safety, and Intraocular Pressure-Lowering Profile of Omidenepag Isopropyl, a Selective, Nonprostaglandin, Prostanoid EP2 Receptor Agonist, in Healthy Japanese and Caucasian Volunteers (Phase I Study)

• Published in: Journal of ocular pharmacology and therapeutics Vol. 35; no. 10; p. 542
• Main Authors: Aihara, Makoto, Lu, Fenghe, Kawata, Hisashi, Tanaka, Yuki, Yamamura, Kenzo, Odani-Kawabata, Noriko, Shams, Naveed K
• Format: Journal Article
• Language: English
• Published: United States 01.12.2019
• Subjects: pharmacokinetics; EP2 receptor agonist; omidenepag isopropyl; phase I; intraocular pressure; glaucoma
• ISSN: 1557-7732
• DOI: 10.1089/jop.2019.0044

Omidenepag isopropyl (OMDI) is a prodrug of OMD, a selective, nonprostaglandin, prostanoid EP2 receptor agonist. This phase I study aimed to investigate the pharmacokinetic properties, safety, and intraocular pressure (IOP)-lowering efficacy of OMDI. Fourteen healthy male volunteers (7 Japanese and 7 Caucasian) 20-35 years of age received 1 drop of OMDI 0.0025% at 9:00 h in both eyes for 7 days. Blood samples were taken predose and up to 8 h postdose on days 1, 3, and 7. The plasma concentration of OMD was determined using high-performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters measured included the maximum plasma concentration ( ) and the half-life ( ) of OMD. IOP, adverse events (AEs), ophthalmic examinations, vital signs, and laboratory values were assessed. for all subjects was reached after 10-15 min and decreased with a of ∼30 min. statistical analyses found significant differences in some pharmacokinetic parameters between Japanese and Caucasian subjects, likely due to differences in body weight. These differences reduced over 7 days of dosing and were not thought to be clinically meaningful. There was no OMD accumulation after 7 days of repeated dosing. Mean IOP was reduced by ∼4-5 mmHg between baseline and 2 h postdose, remaining stable from day 3 onward. All AEs were mild and considered treatment related. Pharmacokinetic parameters of OMD were similar between Japanese and Caucasian subjects. There was no accumulation of OMD after 7 days of dosing. OMDI was well tolerated and demonstrated clinically significant IOP reductions.