March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Safety and Efficacy of a Novel Topical Rho Kinase Inhibitor ATS8535 in vivo
Author Affiliations & Notes
  • Barbara M. Wirostko
    Altheos, South San Francisco, California
  • Hiroshi Umeno
    Research and Development, Asahi Kasei Pharma, Tokyo, Japan
  • Henry Hsu
    Altheos, South San Francisco, California
  • Muralitharan Kengatharan
    Research & Development,
    Altheos, South San Francisco, California
  • Footnotes
    Commercial Relationships  Barbara M. Wirostko, Altheos (C, S); Hiroshi Umeno, Asahi Kasei (E); Henry Hsu, Altheos (E, S); Muralitharan Kengatharan, Altheos (E, S)
  • Footnotes
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Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5079. doi:
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      Barbara M. Wirostko, Hiroshi Umeno, Henry Hsu, Muralitharan Kengatharan; Safety and Efficacy of a Novel Topical Rho Kinase Inhibitor ATS8535 in vivo. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5079.

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

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Purpose: : To determine tolerability and intraocular pressure (IOP) lowering efficacy of a novel topical Rho Kinase (ROCK) inhibitor ATS8535 in unanesthetized normotensive cynomolgus monkeys (NHP) and New Zealand White rabbits (NZW).

Methods: : NZW rabbits (5/group) received a single dose OD topically with ATS8535 (0.008%, 0.08% & 0.2% ophthalmic formulation). NHPs (3-4/group) received a single topical dose OS of ATS8535 (0.008%, 0.08% & 0.2%). IOP was measured every 2hrs from baseline to 10hrs (NHP) or 12hrs (NZW) post dose. In both studies the contralateral control eye received saline. In a separate study, ocular tolerability was assessed in NZW (4 eyes/group) at daily doses of 0.08% to 0.6% given BID for 3 days with safety assessments that included gross exams, eyelid closure, pupil size and biomicroscopy (corneal opacity and congestion of conjunctiva and iris).

Results: : A decline in IOP was observed at 2 hrs post dose in both species with a difference in IOP vs control noted through10 hrs (NHP) and 12hrs (NZW) after instillation of ATS8535. Maximal IOP reduction following single dose administration of ATS8535 was -5.0 mmHg at 0.2% (NHP) and was -7.0mmHg at 0.08% (NZW) between 2-4 hrs post dosing. The mean IOP at baseline for both NHP and NZW was approximately 21.5-22.5 mmHg and did not change significantly over the monitoring period. No significant ocular abnormalities were observed after BID ocular administration in NZW for 3 days other than mild, transient and reversible conjunctival congestion (hyperemia).

Conclusions: : ATS 8535 is effective in lowering IOP topically after a single dose in NZW and NHPs. ATS8535 has a rapid onset of action. Ocular tolerability profile was favorable throughout the study. ATS8535 is a viable therapeutic compound to potentially lower elevated IOP in humans.

Keywords: intraocular pressure • outflow: trabecular meshwork • anterior chamber 

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