June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Pharmacokinetics, Safety and IOP Lowering Profiles of omidenepag isopropyl, a Selective EP2 Agonist in Healthy Japanese and Caucasian Volunteers (Phase I Study)
Author Affiliations & Notes
  • Makoto Aihara
    Ophthalmology, University of Tokyo, Bunkyo-ku, Japan
  • Fenghe Lu
    Santen Inc., Emeryville, California, United States
  • Hisashi Kawata
    Santen Pharmaceutical Co., Ltd., Osaka, Japan
  • Yuki Tanaka
    Santen Pharmaceutical Co., Ltd., Osaka, Japan
  • Kenzo Yamamura
    Santen Pharmaceutical Co.Ltd., Ikoma, Japan
  • Ryo Iwamura
    Ube Industries, Ltd., Ube, Japan
  • Kenji Yoneda
    Ube Industries, Ltd., Ube, Japan
  • Noriko Odani
    Santen Pharmaceutical Co., Ltd., Osaka, Japan
  • Naveed Shams
    Santen Inc., Emeryville, California, United States
  • Footnotes
    Commercial Relationships   Makoto Aihara, Alcon (F), Crewt Medical Systems Co. Ltd. (F), Glaukos Inc. (F), HOYA Co. Ltd. (F), Kowa Pharmaceutical Co. Ltd. (F), Nihon Tenganyaku Kenkyusho Co. Ltd. (F), Otsuka Pharmaceutical Co. Ltd. (F), Pfizer Co. Ltd. (F), Santen Pharmaceutical Co. Ltd. (F), Senju Pharmaceutical Co. Ltd. (F), Wakamoto Pharmaceutical Co. Ltd. (F); Fenghe Lu, Santen Inc. (E); Hisashi Kawata, Santen Pharamceutical Co. Ltd. (E); Yuki Tanaka, Santen Pharmaceutical Co. Ltd. (E); Kenzo Yamamura, Santen Pharmaceutical Co. Ltd. (E); Ryo Iwamura, Use Industries Co. Ltd. (E); Kenji Yoneda, Use Industries Co. Ltd. (E); Noriko Odani, Santen Pharmaceutcal Co. Ltd. (E); Naveed Shams, Santen Inc. (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2104. doi:
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      Makoto Aihara, Fenghe Lu, Hisashi Kawata, Yuki Tanaka, Kenzo Yamamura, Ryo Iwamura, Kenji Yoneda, Noriko Odani, Naveed Shams; Pharmacokinetics, Safety and IOP Lowering Profiles of omidenepag isopropyl, a Selective EP2 Agonist in Healthy Japanese and Caucasian Volunteers (Phase I Study). Invest. Ophthalmol. Vis. Sci. 2017;58(8):2104.

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      © ARVO (1962-2015); The Authors (2016-present)

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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 (Cmax, Tmax, T1/2, and AUCinf) 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: Cmax 37.53 ± 15.52 pg/mL vs 33.31 ± 11.81 pg/mL; AUCinf 24.49 ± 6.43 pg*h/mL vs 20.02 ± 4.81 pg*h/mL; Tmax 0.20 ± 0.08 hours vs 0.18 ± 0.09 hours; T1/2 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.

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