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D. Nickens, J. Mandema, R. Courtney, S. Raber, C. Bosworth; A Model-Based Dose-Response Meta-Analysis of Single Agent Intraocular Pressure (IOP) Therapies Used to Evaluate Efficacy of a Potential New Therapy (PF-03187207) in Glaucoma Patients. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2479.
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Evaluate/characterize the dose-response of PF-03187207 (PF-207) for IOP using a model-based meta-analysis of single agent IOP therapies including prostaglandin analogues and timolol.
Summary level data of randomized controlled clinical trials from published literature, FDA regulatory documents and sponsor reports were used to create a database of single agent IOP lowering compounds. An Emax model was used to characterize the efficacy (IOP change from baseline) profile of the compounds and was evaluated as a function of dose, time of day, time of dose administration (QAM, QPM, BID) and baseline IOP. The models were subsequently updated with data on PF-207 from a dose-ranging (0.003% to 0.04%), active-controlled (latanoprost 0.005%), randomized, double-masked, parallel-group study in adult subjects with primary open-angle glaucoma or ocular hypertension.
The meta-analysis database included 31 trials with summary data on 6516 patients on 30 unique treatment regimens for bimatoprost, latanoprost, travoprost, timolol and placebo. Placebo response was estimated at -2.01 mmHg (baseline IOP 25 mmHg). No significant difference was found in the Emax (estimated at -6.27 mmHg) of the prostaglandin analogues (baseline IOP 25 mmHg). QPM administration had greater IOP reduction when compared to QAM or BID. Values of median effective dose (ED50,%/day) for IOP were estimated as 0.36%, 0.002%, 0.00098%, and 0.00062% for timolol, bimatoprost, latanoprost and travoprost, respectively. The updated model included PF-207 data for 215 randomized patients. ED50 and Emax values for PF-207 were estimated to be 0.0054%/day and -6.90 mmHg, respectively.
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