A Phase 2, Randomized, Dose-Response Trial of Taprenepag Isopropyl (PF-04217329) Versus Latanoprost 0.005% in Open-Angle Glaucoma and Ocular Hypertension

Abstract

Purpose: To evaluate the safety of escalating doses of taprenepag isopropyl (PF-04217329), a selective EP₂ receptor agonist administered as a topical ophthalmic solution, versus its vehicle (Stage I), and dose-response of taprenepag isopropyl alone and in unfixed combination with latanoprost ophthalmic solution 0.005% versus latanoprost alone (Stage II).

Subjects and Methods: Randomized, vehicle- and active-controlled, double-masked, two-stage, dose-finding trial in primary open-angle glaucoma (POAG) or ocular hypertension; first taprenepag isopropyl study in patients (NCT00572455). Study eye: 26 mmHg ≤ intraocular pressure (IOP) <36 mmHg at 8 am and 22 mmHg ≤ IOP <36 mmHg at 10 am, 1 pm, 4 pm. Stage I: 3 cohorts (total n = 67) received 1 drop of taprenepag isopropyl unit dose formulation qPM/eye for 14 days: low dose: 0.0025%, 0.005%, vehicle; middle dose: 0.01%, 0.015%, vehicle; high dose: 0.02%, 0.03%, vehicle. Stage II: 7 groups (total n = 250) received 1 drop of taprenepag isopropyl multidose formulation qPM/eye for 28 days: 0.005%, 0.01%, 0.015% monotherapy; each in unfixed combination with latanoprost 0.005%, or latanoprost monotherapy. Main outcomes: mean change in diurnal IOP, baseline to last visit; adverse events.

Results: Stage I at Day 14: statistically significantly greater IOP reductions were observed at all taprenepag isopropyl doses versus vehicle. Stage II at Day 28: statistically significantly greater IOP reductions were observed at all doses of the unfixed combination versus latanoprost monotherapy. At least 1 treatment-emergent adverse event reported for 29/67 (43.3%) subjects in Stage I and 158/250 (63.2%) in Stage II.

Conclusions: Taprenepag isopropyl significantly reduces IOP in POAG and ocular hypertension. Taprenepag isopropyl monotherapy is comparable to latanoprost 0.005% in reducing IOP. As demonstrated in this report, the activity of taprenepag isopropyl is additive to that of latanoprost 0.005%. Further studies are required to determine whether it shows similar additivity when administered with other ocular antihypertensive medications.

Keywords::

• Intraocular pressure
• Open-angle glaucoma
• Ocular hypertension
• E₂ receptor agonist
• Taprenepag isopropyl

ACKNOWLEDGMENTS

The authors gratefully acknowledge Charles Bosworth, PhD, a former Pfizer Inc employee, for his contributions to the protocol development and the interpretation of the data.

Editorial support, including contributing to the first draft of the paper, revising based on author comments, and styling the paper for journal submission, was provided by Jane G. Murphy, PhD, of Zola Associates and was funded by Pfizer Inc.

Declaration of interest: The research was supported by Pfizer Inc, New York, New York. The sponsor participated in the design, conduct, data management, analysis, and interpretation and in the preparation, review, and approval of the manuscript. R.A. Schachar, S. Raber, R. Courtney, and M. Zhang were employees of Pfizer Inc at the time the study was conducted.