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D. J. Nickens, J. Mandema, S. Raber, R. Schachar, M. Zhang; A Dose-Response Meta-Analysis to Evaluate Intraocular Pressure Reduction of Mono- and Dual-Combination Therapy of PF-04217329, a Selective EP2 Receptor Agonist. Invest. Ophthalmol. Vis. Sci. 2010;51(13):172.
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© ARVO (1962-2015); The Authors (2016-present)
Evaluate IOP reduction for PF-04217329 (PF-329) as monotherapy and combined with latanoprost using a model-based meta-analysis (MBMA) of single and dual agents including prostaglandin (PG) analogs, timolol and dorzolamide.
A MBMA for IOP reduction (change-from-baseline) of single agent therapies was previously presented (IOVS 2009, 50: E-Abst. 2479). The model was extended by adding to the database published randomized controlled trials of a PG + timolol and timolol + dorzolamide, and data on dorzolamide alone and from sponsor reports on latanoprost + timolol. Summary level data were used to characterize dose-response relationships for IOP reduction. Simple drug effects were estimated for therapies without dose-response data (timolol, dorzolamide). The IOP reduction model was then updated with data from a double-masked, phase 2, dose-ranging (0.0025 to 0.03%) efficacy study of PF-329 as single or dual therapy with latanoprost in primary open-angle glaucoma or ocular hypertension.
The meta-analysis included 61 trials with summary data representing 9998 patients on monotherapy and 3520 on dual therapy. The model estimated mean diurnal IOP reduction for PF-329 monotherapy was similar to PGs alone. A statistically significant synergistic effect of PF-329 + latanoprost was observed (p<0.05). Model-based predictions showed PF-329 (0.005 to 0.01%) + latanoprost has a high probability (≥80%) of providing a 1.5 mmHg improvement in mean diurnal IOP reduction over latanoprost 0.005% alone. The predicted mean diurnal IOP reduction for PF-329 (0.005 to 0.01%) + latanoprost has at least a 0.6 mmHg improvement over latanoprost + timolol.
Model-based predictions indicate that PF-329 monotherapy significantly reduces IOP similar to marketed PGs (latanoprost, travoprost, bimatoprost). Synergism between PF-329 and latanoprost is supportive of a novel mechanism of action.
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