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Barbara M. Wirostko, H Umeno, Henry H. Hsu, Muralitharan Kengatharan; Safety and Efficacy of a Novel Topical Rho Kinase Inhibitor ATS907 in Normotensive Cynomolgus Monkeys. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3096.
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© ARVO (1962-2015); The Authors (2016-present)
To determine tolerability and intraocular pressure (IOP) lowering efficacy of a novel topical Rho Kinase (ROCK) inhibitor ATS907 in unanesthetized normotensive (NT) cynomolgus Monkeys. Single dose and repeat 14 day (BID) dose ranging studies were conducted.
Three to four NT monkeys per dose received a single topical dose OS of ATS907. Doses included 0.05% and 0.5% ATS907 or 0.005% latanoprost in 50ul. IOP was measured at baseline and 2, 4, 6, 8, and 10 hrs post dose. The repeat dose study utilized 3 NT monkeys per dose given 0.05% and 0.2% ATS907 doses, (30 ul BID) OD for 14 days. IOP was measured on the 1st, 4th, 9th and 14th days of administration immediately before the morning dose and 3, 6, 9, 12, and 24 hours thereafter. In both studies the contralateral control eye received saline. In a separate study, tolerability was assessed daily at doses 0.1% to 3.0% given BID for 14 days with gross exams and biomicroscopy, and eventual histopathology. Eyelid closure, corneal opacity, congestion of conjunctiva and iris, and pupil size were evaluated.
A decline in IOP was observed starting 2 hrs post dose. A difference in IOP vs control continued through 10 hrs after instillation of ATS907. Maximal IOP reduction following single dose administration of ATS907 0.05% and 0.5% were -3.7 mmHg and -4.65 mmHg, respectively compared with 2.43 mmHg seen with latanoprost 0.005%. The mean IOP from 2 hrs to 10 hrs after dosing for the control eyes was 21.43 -21.83 mmHg. With repeat dosing, a drop in IOP occurred on day 1 and was maintained through day 14 with both doses with a mean difference of -2.3 to - 3.9 mmHg vs control. No significant ocular abnormalities were observed after either single or repeat dosing across intented therapeutic doses with sufficient safety margins at any observation point.
ATS 907 is effective in lowering IOP topically after a single dose and after repeat dosing out to 14 days. ATS 907 has an early onset of action. Repeat dosing maintained the IOP hypotensive efficacy through to 14 days. Tolerability profile was favorable throughout the study. ATS 907 is a viable therapeutic compound to potentially lower elevated IOP in humans.
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