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R. A. Schachar, S. Raber, R. Courtney, M. Zhang, C. Bosworth; Dose-Escalating, Double-Masked, Vehicle-Controlled Trial of the IOP-Reducing Effect of the EP2 Agonist PF-04217329. Invest. Ophthalmol. Vis. Sci. 2010;51(13):175.
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To assess the safety and efficacy of escalating doses of PF-04217329, an EP2 agonist, versus its vehicle in subjects diagnosed with ocular hypertension or primary open-angle glaucoma.
Three cohorts of subjects (n=67) were randomly assigned to receive one drop of PF-04217329 daily (qPM) in each eye for 14 days: Cohort 1 - 0.0025%, 0.005%, or vehicle; Cohort 2 - 0.01%, 0.015%, or vehicle; and Cohort 3 - 0.02%, 0.03%, or vehicle. Safety data were reviewed prior to enrollment of the next higher dose cohort. The study eye was required to have: 26 mmHg ≤ IOP < 36 mmHg at 8AM and 22 mmHg ≤ IOP < 36 mmHg at 10AM, 1PM and 4PM. Subjects were washed out of all previous ocular antihypertensive medications. An analysis of covariance (ANCOVA) was used to estimate the difference in mean diurnal IOP reduction on Day 14 between each concentration of PF-04217329 and its vehicle.
On Day 14, greater and statistically significant IOP reductions were observed with all doses of PF-04217329 compared to its vehicle. Least squares (LS) mean differences ranged from 3.02 mmHg to 6.56 mmHg in the study eye. Twenty nine (43.3%) of 67 subjects experienced at least one treatment emergent adverse event. Photophobia +/- iritis was reported in 10%, 44% and 67% of subjects receiving the higher doses, 0.015%, 0.02% and 0.03%, of PF-04217329, respectively. Statistically significant increases in corneal thickness from baseline [LS mean range: 15.3 µm to 23.7 µm] were observed with 0.005%, 0.02% and 0.03% PF-04217329 in at least one eye.
PF-04217329 significantly reduces IOP more than its vehicle across the dose range 0.0025% to 0.03%. Doses >0.015% are associated with higher incidence of ocular adverse effects. Additional dose-response and 24-hour diurnal IOP studies of PF-04217329 in ocular hypertension and primary open-angle glaucoma subjects are ongoing.
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