Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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.
Clinical Trial: :
www.clinicaltrials.gov NCT00441883
Keywords: clinical (human) or epidemiologic studies: biostatistics/epidemiology methodology • intraocular pressure